Mass spectrometry-based proteomic profiling of extracellular vesicle proteins in diabetic and non-diabetic ischemic stroke patients: a case-control study.

Acute ischemic stroke is the most common cause of neurologic dysfunction caused by focal brain ischemia and tissue injury. Diabetes is a major risk factor of stroke, exacerbating disease management and prognosis. Therefore, discovering new diagnostic markers and therapeutic targets is critical for stroke prevention and treatment. Extracellular vesicles (EVs), with their distinctive properties, have emerged as promising candidates for biomarker discovery and therapeutic application. This case-control study utilized mass spectrometry-based proteomics to compare EVs from non-diabetic stroke (nDS = 14), diabetic stroke (DS = 13), and healthy control (HC = 12) subjects. Among 1288 identified proteins, 387 were statistically compared. Statistical comparisons using a general linear model (log2 foldchange ≥0.58 and FDR-p≤0.05) were performed for nDS vs HC, DS vs HC, and DS vs nDS. DS vs HC and DS vs nDS comparisons produced 123 and 149 differentially expressed proteins, respectively. Fibrinogen gamma chain (FIBG), Fibrinogen beta chain (FIBB), Tetratricopeptide repeat protein 16 (TTC16), Proline rich 14-like (PR14L), Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKE), Biorientation of chromosomes in cell division protein 1-like 1 (BD1L1), and protein PR14L exhibited significant differences in the DS group. The pathway analysis revealed that the complement system pathways were activated, and blood coagulation and neuroprotection were inhibited in the DS group (z-score ≥2; p ≤ 0.05). These findings underscore the potential of EVs proteomics in identifying biomarkers for stroke management and prevention, warranting further clinical investigation.

Comprehensive Characterization of Protein Turnover by Comparative SILAC Labeling Analysis in 3T3-L1.

A balance between the synthesis and degradation of proteins is referred to as protein turnover, which is crucial for cellular protein homeostasis. Proteome-wide analysis of protein turnover in adipocytes, which are well-known for their role in energy storage and their link to obesity and metabolism disorders, is yet to be conducted. Thus, with this objective in mind, our investigation utilized a comparative analysis of time-dependent SILAC labeling to assess protein turnover in 3T3-L1 adipocytes, spanning a period of 0 to 144 h. We observed that relatively faster or slower protein half-lives in several protein groups were associated with the PPARγ signaling pathway, energy metabolism, extracellular matrix, ubiquitin-proteasome system, RNA splicing, Golgi complex, and lysosome. It is anticipated that these protein half-life profiles will provide greater clarity on the life cycle of adipocyte proteome and shed light on how they maintain protein homeostasis.

Flavin Adenine Dinucleotide (FAD) and Pyridoxal 5'-Phosphate (PLP) Bind to Sox9 and Alter the Expression of Key Pancreatic Progenitor Transcription Factors.

Cofactor flavin adenine dinucleotide (FAD), a compound with flavin moiety and a derivative of riboflavin (vitamin B2), is shown to bind to Sox9 (a key transcription factor in early pancreatic development) and, subsequently, induce a large increase in markers of pancreatic development, including Ngn3 and PTF1a. Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, also binds to Sox9 and results in a similar increase in pancreatic development markers. Sox9 is known to be specifically important for pancreatic progenitors. Previously, there was no known link between FAD, PLP, or other co-factors and Sox9 for function. Thus, our findings show the mechanism by which FAD and PLP interact with Sox9 and result in the altered expression of pancreatic progenitor transcription factors involved in the pancreas development.

[The Effect of COVID-19 on Pediatric Intussusception: A Retrospective Study of a Single Center in South Korea with 10-Year Experience]. / 코로나바이러스감염증­2019 ìœ í–‰ 후 소아 장중첩증의 변화: 단일기관 10ë „ 의무 기록을 이용한 연구.

Purpose: To evaluate the effect of the emergence of coronavirus disease-19 (COVID-19) on pediatric intussusception. Materials and Methods: Patients (< 18 years) who were diagnosed with intussusception and received enema reduction from 2011 to 2020 were included. We reviewed the demographics, yearly/monthly/seasonal incidence of intussusception, method and failure rate of enema reduction, recurrence rate of intussusception, surgical record, and pathologic report. Subsequently, we investigated the differences in mean age, failure rate of enema reduction, and recurrence rate of intussusception between the cases in 2020 and those in the period from 2011 to 2019. Results: A total of 859 enema reductions were performed during the past decade, more in males and in the age < 1 year (mean age, 22.2 months). The yearly incidence was highest in 2014 and lowest in 2020, and the monthly incidence was highest on December and September. The cases in 2020 (n = 27) had a lower mean age (18.1 months vs. 22.8 months), higher failure rate of enema reduction (7.4% vs. 2.4%), and higher recurrence rate of intussusception (14.8% vs 7.3%) compared with those that occurred between 2011 and 2019 (n = 832). However, these results did not show statistical significance (p = 0.07, p = 0.15, p = 0.14, respectively). Conclusion: With the emergence of COVID-19, the number of enema reductions was remarkably decreased with a lower mean age, higher failure rate, and higher recurrence rate.

Epidemiology and Long-Term Adverse Outcomes in Korean Patients with Congenital Adrenal Hyperplasia: A Nationwide Study.

BACKGROUND: Previous studies on the epidemiology and complications of congenital adrenal hyperplasia (CAH) were conducted in Western countries and in children/adolescents. We aimed to explore the epidemiology of CAH, as well as the risk of comorbidities and mortality, in a Korean nationwide case-control study. METHODS: CAH patients (n=2,840) were included between 2002 and 2017 from the National Health Insurance Service database and the Rare Intractable Disease program. CAH patients were compared, at a 1:10 ratio, with age-, sex-, and index year-matched controls (n=28,400). RESULTS: The point prevalence of CAH patients in Korea was 1 in 18,745 persons in 2017. The annual incidence rate declined between 2003 and 2017 from 3.25 to 0.41 per 100,000 persons. CAH patients were at elevated risk for cardiovascular disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.4 to 1.9), stroke (OR, 1.7; 95% CI, 1.3 to 2.0), diabetes mellitus (OR, 2.8; 95% CI, 2.6 to 3.1), dyslipidemia (OR, 2.4; 95% CI, 2.2 to 2.6), and psychiatric disorders (OR, 1.5; 95% CI, 1.3 to 1.6). Fracture risk increased in CAH patients aged over 40 years (OR, 1.4; 95% CI, 1.1 to 1.7). CAH patients were at higher risk of mortality than controls (hazard ratio, 1.6; 95% CI, 1.3 to 2.0). CONCLUSION: Our nationwide study showed a recent decline in the incidence of CAH and an elevated risk for cardiovascular, metabolic, skeletal, and psychiatric disorders in CAH patients. Lifelong management for comorbidity risk is a crucial component of treating CAH patients.

Proteomic profiling of metformin effects in 3T3-L1 adipocytes by SILAC-based quantification.

Metformin is a common and generally the first medication prescribed for treatment of type 2 diabetes. Its mechanism involves affecting pathways that regulate glucose and lipid metabolism in metabolic cells such as that of muscle and liver cells. In spite of various studies exploring its effects, the proteome changes in adipocytes in response to metformin remains poorly understood. In this study, we performed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic profiling to study the effects of metformin specifically on 3T3-L1 adipocytes. We define proteins that exhibited altered levels with metformin treatment, 400 of them showing statistically significant changes in our study. Our results suggest that metformin affects not only the PPAR signaling pathway, as well as glucose and lipid metabolism, but also protein folding, endoplasmic reticulum stress, negative regulation of appetite, and one-carbon folate metabolism in adipocytes. This proteomic investigation provides important insight into effects of metformin in adipocytes.

Impact of acute kidney injury on graft outcomes of deceased donor kidney transplantation: A nationwide registry-based matched cohort study in Korea.

BACKGROUND: Favorable long-term and short-term graft survival and patient survival after kidney transplantation (KT) from deceased donors with acute kidney injury (AKI) have been reported. However, few studies have evaluated effects of donor AKI status on graft outcomes after KT in Asian population. Thus, the purpose of this study was to evaluate graft function after KTs from donors with AKI compared to matched KTs from donors without AKI using a multicenter cohort in Korea. METHODS: We analyzed a total of 1,466 KTs collected in Korean Organ Transplant Registry between April 2014 and December 2017. KTs from AKI donors (defined as donors with serum creatinine level ≥ 2 mg/dL) and non-AKI donors (275 cases for each group) were enrolled using a 1:1 propensity score matching. Graft outcomes including graft and patient survival, delayed graft function (DGF), rejection rate, and serially measured estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: After propensity matching, KTs from AKI donors showed higher rate of DGF (44.7% vs. 24.0%, p < 0.001). However, the rejection rate was not significantly different between the two groups (KTs from AKI donors vs. KTs from non-AKI donors). eGFRs measured after 6 months, 1 year, 2 years and 3 years were not significantly different by donor AKI status. With median follow-up duration of 3.52 years, cox proportional hazards models revealed hazard ratio of 0.973 (95% confidence interval [CI], 0.584 to 1.621), 1.004 (95% CI, 0.491 to 2.054) and 0.808 (95% confidence interval [CI], 0.426 to 1.532) for overall graft failure, death-censored graft failure and patient mortality, respectively, in KTs from AKI donors compared to KTs from non-AKI donors as a reference. CONCLUSIONS: KTs from AKI donors showed comparable outcomes to KTs from non-AKI donors, despite a higher incidence of DGF. Results of this study supports the validity of using kidneys from deceased AKI donors in Asian population.

ACBD3 modulates KDEL receptor interaction with PKA for its trafficking via tubulovesicular carrier.

BACKGROUND: KDEL receptor helps establish cellular equilibrium in the early secretory pathway by recycling leaked ER-chaperones to the ER during secretion of newly synthesized proteins. Studies have also shown that KDEL receptor may function as a signaling protein that orchestrates membrane flux through the secretory pathway. We have recently shown that KDEL receptor is also a cell surface receptor, which undergoes highly complex itinerary between trans-Golgi network and the plasma membranes via clathrin-mediated transport carriers. Ironically, however, it is still largely unknown how KDEL receptor is distributed to the Golgi at steady state, since its initial discovery in late 1980s. RESULTS: We used a proximity-based in vivo tagging strategy to further dissect mechanisms of KDEL receptor trafficking. Our new results reveal that ACBD3 may be a key protein that regulates KDEL receptor trafficking via modulation of Arf1-dependent tubule formation. We demonstrate that ACBD3 directly interact with KDEL receptor and form a functionally distinct protein complex in ArfGAPs-independent manner. Depletion of ACBD3 results in re-localization of KDEL receptor to the ER by inducing accelerated retrograde trafficking of KDEL receptor. Importantly, this is caused by specifically altering KDEL receptor interaction with Protein Kinase A and Arf1/ArfGAP1, eventually leading to increased Arf1-GTP-dependent tubular carrier formation at the Golgi. CONCLUSIONS: These results suggest that ACBD3 may function as a negative regulator of PKA activity on KDEL receptor, thereby restricting its retrograde trafficking in the absence of KDEL ligand binding. Since ACBD3 was originally identified as PAP7, a PBR/PKA-interacting protein at the Golgi/mitochondria, we propose that Golgi-localization of KDEL receptor is likely to be controlled by its interaction with ACBD3/PKA complex at steady state, providing a novel insight for establishment of cellular homeostasis in the early secretory pathway.

Trajectories in glycated hemoglobin and body mass index in children and adolescents with diabetes using the common data model.

We evaluated trajectories of glycated hemoglobin (HbA1c) levels and body mass index z-scores (BMIz) for 5 years after diagnosis among Korean children and adolescents with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the common data model. From the de-identified database of three hospitals, 889 patients < 15 years of age diagnosed with T1D or T2D (393 boys, 664 T1D patients) were enrolled. Diagnosis was defined as first exposure to antidiabetic drug at each center. Compared with T2D patients, T1D patients had lower BMIz at diagnosis (- 0.4 ± 1.2 vs. 1.5 ± 1.4, p < 0.001) and 3 months (- 0.1 ± 1.0 vs. 1.5 ± 1.5, p < 0.001), and higher HbA1c levels at diagnosis (10.0 ± 2.6% vs. 9.5 ± 2.7%, p < 0.01). After 3 months, HbA1c levels reached a nadir of 7.6% and 6.5% in T1D and T2D patients, respectively, followed by progressive increases; only 10.4% of T1D and 29.7% of T2D patients achieved the recommended HbA1c target (< 7.0%) at 60 months. T1D patients showed consistent increases in BMIz; T2D patients showed no significant change in BMIz during follow-up. Peri-pubertal girls with T1D had higher HbA1c and BMIz values. Achieving optimal glycemic control and preventing obesity should be emphasized in pediatric diabetes care.

Quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer (ASPIRE): A long-term prospective, multicentre, cohort study.

BACKGROUND: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery. METHODS: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525). FINDINGS: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval  [CI], -1•3 to 9•7, p = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6, p = 0•0052), micturition symptoms (-8•0 points; 95% CI, -14•1 to -1•8, p = 0•0108), male sexual problems (-19•9 points; 95% CI, -33•1 to -6•7, p = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8, p = 0•0155), and worse urinary symptoms (-5•4 points on a 35-point scale; 95% CI, -8•0 to -2•7, p < 0•0001). The 5-year overall survival was worse with abdominoperineal resection in unadjusted (92•2% vs 80•9%; difference 11•3%, hazard ratio 2•38; 95% CI, 1•27 to 4•46, p = 0•0052), but did not differ after adjustment. INTERPRETATION: In this long-term prospective study, abdominoperineal resection failed to meet the superiority to sphincter preservation surgery in terms of quality of life. Although the global quality of life scores did not differ between groups, this study suggests that sphincter preservation surgery can be an acceptable alternative to abdominoperineal resection for low rectal cancer, offering a better quality of life and sexual-urinary functions, with no increased oncological risk even after 3 years. FUNDING: Seoul National University Bundang Hospital, Korea.

Analysis of Sagittal Position Changes of the Condyle After Mandibular Setback Surgery Across the Four Different Types of Plating Systems.

ABSTRACT: The authors analyzed the three-dimensional postoperative condylar position change across the plating systems. This retrospective study was conducted with the patients who underwent bilateral sagittal split ramus osteotomy with setback surgery. The condylar change was analyzed from preoperative cone-beam computed tomography to postoperative 1 month (T1) and postoperative 6 months (T2) using superimposition software, automatically merging based on the anterior cranial base. The condylar changes during T1 and T2 were analyzed across the four types of plates (4-hole sliding, heart-shaped, 3-hole sliding, and 4-hole conventional) Mean intraclass correlation coefficient values were consistently high for each measurement (>0.850). During T1, the conventional plate had a decreased condylar anterior distance when compared with the 3-hole sliding plate (P = 0.032). During T2, the conventional plate had an increased condylar posterior distance when compared with the 3-hole sliding plate (P = 0.031). Superimposition software based on the anterior cranial base could be available for measurement of condylar position with highly reproducible results. After bilateral sagittal split ramus osteotomy, the 3-hole sliding plate could effectively compensate for the anterior displacement of the condyle compared to other plates.

Classification of postoperative edema based on the anatomic division with mandibular third molar extraction.

PURPOSE: Several investigations have been performed for a postoperative edema after extraction, but the results have been controversial due to low objectivity or poorly reproducible assessments of the edema. The aim of this study was to suggest a classification and patterns of postoperative edema according to the anatomical division associated with extraction of mandibular third molar as a qualitative evaluation method. METHODS: This study was conducted forty-four mandibular third molars extracted and MRI was taken within 48 h after extraction. The postoperative edema space was classified by MRI (one anatomic component-buccinator muscle-and four fascial spaces-supra-periosteum space, buccal space, parapharyngeal space, and lingual space), and evaluated independently by two examiners. The inter-examiner reliability was calculated using Kappa statistics. RESULTS: The evaluation of buccinator muscle edema showed good agreement and the fascial spaces showed constant high agreement. The incidence of postoperative edema was high in the following order: supra-periosteum space (75.00%), buccinator muscle (68.18%), parapharyngeal space (54.55%), buccal space (40.91%), and lingual space (25.00%). CONCLUSION: Postoperative edema could be assessed clearly by each space, which showed a different tendency between the anatomic and fascial spaces.

Development and validation of a difficulty index for mandibular third molars with extraction time.

OBJECTIVES: : This study aimed to validate the effectiveness of a recently proposed difficulty index for removal of impacted mandibular third molars based on extraction time and suggest a modified difficulty index including the presence of pathologic conditions associated with third molars. MATERIALS AND METHODS: This retrospective study enrolled 65 male patients younger than 25 years with third molars. Extraction time was calculated from start of the incision to the last suture. The difficulty scores for third molars were based on spatial relationship (1-5 points), depth (1-4 points), and ramus relationship (1-3 points) using cone-beam computed tomography. The difficulty index was defined as follows: I (3-4 points), II (5-7 points), III (8-10 points), and IV (11-12 points). The modified difficulty score was calculated by adding one point to the difficulty score if the third molar was associated with a pathologic condition. Two modified difficulty indices, based on the presence of pathologic conditions, were as follows: the half-level up difficulty index (HDI) and the one-level up difficulty index (ODI) from the recently proposed difficulty index. RESULTS: The correlations between extraction time and difficulty index and or modified difficulty indices were significant (P<0.001). The correlation coefficient between extraction time and difficulty index was 0.584. The correlation coefficients between extraction time and HDI and ODI were 0.728 and 0.764, respectively. CONCLUSION: Extraction time of impacted third molars exhibited a moderate correlation with difficulty index and was strongly correlated with the modified indices. Considering the clinical implications, the difficulty index of surgical extraction should take into consideration the pathologic conditions associated with third molars.

Comparative Proteomic Profiling of 3T3-L1 Adipocyte Differentiation Using SILAC Quantification.

Adipocyte differentiation is a general physiological process that is also critical for metabolic syndrome. In spite of extensive study in the past two decades, adipogenesis is a still complex cellular process that is accompanied by complicated molecular mechanisms. Here, we performed SILAC-based quantitative global proteomic profiling of 3T3-L1 adipocyte differentiation. We report protein changes to the proteome profiles, with 354 proteins exhibiting significant increase and 56 proteins showing decrease in our statistical analysis. Our results show that adipocyte differentiation is involved not only in metabolic processes by increasing TCA cycle, fatty acid synthesis, lipolysis, acetyl-CoA production, antioxidants, and electron transport, but also in nicotinamide metabolism, cristae formation, mitochondrial protein import, and Ca2+ transport into mitochondria and ER. A search for Chromosome-Centric Human Proteome Project (C-HPP) using neXtprot highlighted one protein with a protein existence uncertain (PE5) and 17 proteins as functionally uncharacterized protein existence 1 (uPE1). This study provides quantitative information on proteome changes in adipogenic differentiation, which is helpful in improving our understanding of the processes of adipogenesis.

Association of maxillary dental developmental abnormality with precocious puberty: a case-control study.

BACKGROUND: Dental studies of precocious puberty have focused on examination of jaw and dentition growth. The aim of the study was to analyze the relationship between precocious puberty and maxillary dental developmental abnormalities (DDAs). METHODS: This retrospective study was conducted on the Korean patients in whom dental panoramic and hand-wrist radiographs had been taken before they were 15 years of age. The maxillary DDAs were assessed as mesiodens, congenital missing teeth, peg-shape lateral incisors, or impacted teeth. The chronological ages of the control group members were within the normal range of the hand-wrist bone age. Others with a peak luteinizing hormone of ≥ 5 and < 5 IU/L were allocated to central precocious puberty (CPP) and peripheral precocious puberty (PPP), respectively. RESULTS: Of the enrolled 270 patients, 195, 52, and 23 were allocated to the control, CPP, and PPP groups, respectively. The maxillary DDAs were significantly more prevalent in the CPP group than in the other groups. Among those with maxillary DDA, the mesiodens predominated. Age- and sex-adjusted multivariate analysis revealed maxillary DDA (odds ratio, 3.36; 95% CI, 1.60-7.05) and especially mesiodens (odds ratio, 5.52; CI, 2.29-13.28) to be significantly associated with CPP. CONCLUSIONS: Maxillary DDAs were significantly more prevalent in the CPP group than in the PPP or control groups. Among the many types of maxillary DDAs, mesiodens was significantly associated with CPP and may be considered a predictor of the development of CPP.

Helicobacter pylori Eradication Induced Constant Decrease in Interleukin- 1B Expression over More Than 5 Years in Patients with Gastric Cancer and Dysplasia.

Background/Aims: Helicobacter pylori (Hp) suppresses gastric acid secretion by repressing the expression of the H+, K+-adenosine triphosphatase (H+, K+-ATPase) and stimulating interleukin-1 (IL-1ß; encoded by IL-1B). This study was aimed at evaluating the expression of the H+, K+-ATPase and IL-1ß after Hp eradication. Methods: Two hundred twentyone subjects were categorized as Hp-negative (n=84) or Hppositive (n=137) according to the results of Hp tests (histology, CLO test, culturing, and serology). The mRNA expression levels of IL-1B and ATP4A (the gene encoding the α-subunit of H+, K+-ATPase) were measured in biopsy specimens from the gastric corpus using real-time polymerase chain reaction. Results: The Hp-positive group had significantly higher IL-1B mRNA levels than the whole Hp-negative group and the intestinal metaplasia (IM)-negative subgroup. After Hp eradication, the difference between the Hp-negative and Hperadicated groups disappeared, including in the IM-negative subgroup. The IL-1B mRNA level did not significantly change from the baseline level. Within the gastric cancer (GC)/dysplasia subgroup, the IL-1B mRNA levels at 1, 2, 3-4, and ≥5 years after Hp eradication were significantly lower than the baseline level. The difference in ATP4A mRNA levels between the Hp-negative and Hp-positive groups was not significant at baseline, and the changes in the ATP4A mRNA levels after Hp eradication compared to the baseline levels in the whole group and subgroups stratified by the presence of IM and GC/dysplasia were not significant. Conclusions: Infection with Hp has an effect on the level of IL-1B mRNA in IM-negative subjects. The continuous reduction in the IL-1B mRNA level in patients with GC/dysplasia after Hp eradication contributes to the prevention of metachronous GC after Hp eradication.

Prior statin therapy and mortality among critically ill patients: a systemic review and meta-analysis of cohort studies.

The effect of prior statin exposure in critically ill patients remains controversial and has not been established in previous cohort studies. We performed a systematic review of previous cohort studies to evaluate the association of prior statin therapy with mortality in critically ill patients and conducted a meta-analysis. The MEDLINE, EMBASE, and Cochrane CENTRAL databases, from their inception to January 7, 2020, were used for this study. Statin users were defined as patients prescribed statin regularly before intensive care unit admission or diagnosis of a specific disease, such as sepsis. The Cochran chi-square test and I statistics were used to determine heterogeneity between studies. In total, 199,985 critically ill patients from nine studies (44,582 statin users and 155,403 non-statin users) were included in the meta-analysis. According to the random effect model, the 30-day mortality of statin users was 31% lower than that of non-statin users (hazard ratio: 0.69, 95% confidence interval: 0.56 to 0.85). This association was similar in atorvastatin users and simvastatin users. However, hospital mortality in statin users was not significantly associated with that in non-statin users [odds ratios (ORs): 0.71, 95% CI: 0.42 to 1.21]. This study showed that there was a beneficial association of prior statin therapy with 30-day mortality in critically ill patients. However, there was no significant association with hospital mortality. Additional prospective cohort studies with a large sample size should be performed to confirm these findings.

Prediction of Apnea-Hypopnea Index Using Sound Data Collected by a Noncontact Device.

OBJECTIVE: To predict the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea (OSA) using data from breathing sounds recorded using a noncontact device during sleep. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral hospital. SUBJECT AND METHODS: Audio recordings during sleep were performed using an air-conduction microphone during polysomnography. Breathing sounds recorded from all sleep stages were analyzed. After noise reduction preprocessing, the audio data were segmented into 5-second windows and sound features were extracted. Estimation of AHI by regression analysis was performed using a Gaussian process, support vector machine, random forest, and simple linear regression, along with 10-fold cross-validation. RESULTS: In total, 116 patients who underwent attended, in-laboratory, full-night polysomnography were included. Overall, random forest resulted in the highest performance with the highest correlation coefficient (0.83) and least mean absolute error (9.64 events/h) and root mean squared error (13.72 events/h). Other models resulted in somewhat lower but similar performances, with correlation coefficients ranging from 0.74 to 0.79. The estimated AHI tended to be underestimated as the severity of OSA increased. Regarding bias and precision, estimation performances in the severe OSA subgroup were the lowest, regardless of the model used. Among sound features, derivative of the area methods of moments of overall standard deviation demonstrated the highest correlation with AHI. CONCLUSION: AHI was fairly predictable by using data from breathing sounds generated during sleep. The prediction model may be useful not only for prescreening but also for follow-up after treatment in patients with OSA.

Golgin45-Syntaxin5 Interaction Contributes to Structural Integrity of the Golgi Stack.

The unique stacked morphology of the Golgi apparatus had been a topic of intense investigation among the cell biologists over the years. We had previously shown that the two Golgin tethers (GM130 and Golgin45) could, to a large degree, functionally substitute for GRASP-type Golgi stacking proteins to sustain normal Golgi morphology and function in GRASP65/55-double depleted HeLa cells. However, compared to well-studied GM130, the exact role of Golgin45 in Golgi structure remains poorly understood. In this study, we aimed to further characterize the functional role of Golgin45 in Golgi structure and identified Golgin45 as a novel Syntaxin5-binding protein. Based primarily on a sequence homology between Golgin45 and GM130, we found that a leucine zipper-like motif in the central coiled-coil region of Golgin45 appears to serve as a Syntaxin5 binding domain. Mutagenesis study of this conserved domain in Golgin45 showed that a point mutation (D171A) can abrogate the interaction between Golgin45 and Syntaxin5 in pull-down assays using recombinant proteins, whereas this mutant Golgin45 binding to Rab2-GTP was unaffected in vitro. Strikingly, exogenous expression of this Syntaxin5 binding deficient mutant (D171A) of Golgin45 in HeLa cells resulted in frequent intercisternal fusion among neighboring Golgi cisterna, as readily observed by EM and EM tomography. Further, double depletion of the two Syntaxin5-binding Golgin tethers also led to significant intercisternal fusion, while double depletion of GRASP65/55 didn't lead to this phenotype. These results suggest that certain tether-SNARE interaction within Golgi stack may play a role in inhibiting intercisternal fusion among neighboring cisternae, thereby contributing to structural integrity of the Golgi stack.

Impact of H3.3 K27M Mutation on Prognosis and Survival of Grade IV Spinal Cord Glioma on the Basis of New 2016 World Health Organization Classification of the Central Nervous System.

BACKGROUND: Spinal cord glioma grade IV is a rare, diffuse midline glioma. H3 K27M-mutant was classified in a different entity in the 2016 World Health Organization (WHO) classification recently. No reports about prognosis of spinal cord glioma grade IV are available yet. OBJECTIVE: To analyze the prognostic factors for spinal cord glioma grade IV. METHODS: Twenty-five patients with spinal cord glioma of grade IV who underwent surgery in a single institute were selected. All grade IV spinal cord glioma histologically confirmed as glioblastoma or "diffuse midline glioma with H3 K27M-mutant" by the 2016 WHO classification of the central nervous system were included. Basic demographics, treatment modalities, and pathological tumor molecular profiles were investigated for prognosis. RESULTS: Mean age was 39.1 yr; male to female ratio was 18 : 7. Tumor was located in thoracic cord (53.3%), cervical cord (40%), and lumbar area (6.7%). Median overall survival was 37.1 mo; median disease-free survival was 18.5 mo. Treatment modality showed no statistical difference. Only K27M profile showed significant prognostic value, 20 patients (80%) showed K27M mutation positive, K27M mutation patients showed longer overall survival (40.07 mo) than K27M negative patients (11.63 mo, P < .0001), and disease-free survival (20.85 vs 8.72 mo, P = .0241). CONCLUSION: This study is the first and largest report of the prognosis of primary spinal cord grade IV glioma using the new WHO classification. This study reported survival analysis and prognostic factors, and revealed that H3.3 K27M mutation is not a major poor prognostic factor. Further studies to explore K27M mutations needed for risk stratification and therapy optimization.