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We sought to evaluate the clinical implication of LAE based on left atrial anterior–posterior (LA AP) dimension or LA volume index (LAVI) in Korean patients with atrial fibrillation (AF). We enrolled 8159 AF patients from the CODE-AF registry. The primary outcome was rate of stroke or systemic embolism (SSE). The prevalence of mild, moderate, and severe LAE by LA AP dimension was 30.6%, 18.5%, and 21.4%, and by LAVI (available in 5808 patients) was 15.7%, 12.5% and 37.8%, respectively. Compared with no or mild LAE, patients with significant LAE (moderate to severe LAE, n = 3258, 39.9%) were associated with a higher rate of SSE (2.5% vs. 1.4%, P = 0.001). Multivariable analysis suggested presence of significant LAE by LA AP dimension was associated with a higher risk of SSE in the overall population (HR 1.57, 95% CI: 1.14–2.17, P = 0.005) and in patients using anticoagulants (n = 5836, HR 1.79, 95% CI: 1.23–2.63, P = 0.002). Patients with significant LAE by LAVI were also at higher risk of SSE (HR 1.58, 95% CI: 1.09–2.29, P = 0.017). In conclusion, significant LAE by LA dimension or LAVI was present in 39.9% and 50.2% of AF patients, respectively, and was associated with a higher rate of SSE.

Background: Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emergedWe aimed to compare these two methods in terms of short-term outcomes and cost analysis under Korean medical insurance system. Materials and methods: 62 patients with high-risk rectal cancer underwent either SCRT or LCRT followed by total mesorectal excision (TME) and classified into two groups. Twenty-seven patients received 5 Gy × 5 with two cycles of XELOX (capecitabine 1,000 mg/m2 and oxaliplatin 130 mg/m2 every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation was assessed between the two groups. Result: Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p = 0.223). The 2-year recurrence-free survival rate did not show significant difference between the groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p = 0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18,787 vs. $22,203, p < 0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11,955 vs. $19,641, p < 0.001) compared to LCRT. SCRT has been shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. Conclusion: SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction of total cost of care and distinguished cost-effectiveness compared to LCRT.

The cortical actin cytoskeleton plays a critical role in maintaining intestinal epithelial integrity, and the loss of this architecture leads to chronic inflammation, as seen in inflammatory bowel disease (IBD). However, the exact mechanisms underlying aberrant actin remodeling in pathological states remain largely unknown. Here, we show that a subset of patients with IBD exhibits substantially higher levels of tripartite motif-containing protein 40 (TRIM40), a gene that is hardly detectable in healthy individuals. TRIM40 is an E3 ligase that directly targets Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), an essential kinase involved in promoting cell-cell junctions, markedly decreasing the phosphorylation of key signaling factors critical for cortical actin formation and stabilization. This causes failure of the epithelial barrier function, thereby promoting a long-lived inflammatory response. A mutant TRIM40 lacking the RING, B-box, or C-terminal domains has impaired ability to accelerate ROCK1 degradation-driven cortical actin disruption. Accordingly, Trim40-deficient male mice are highly resistant to dextran sulfate sodium (DSS)-induced colitis. Our findings highlight that aberrant upregulation of TRIM40, which is epigenetically silenced under healthy conditions, drives IBD by subverting cortical actin formation and exacerbating epithelial barrier dysfunction.

Canonically, complement is a serum-based host defense system that protects against systemic microbial invasion. Little is known about the production and function of complement components on mucosal surfaces. Here we show gut complement component 3 (C3), central to complement function, is regulated by the composition of the microbiota in healthy humans and mice, leading to host-specific gut C3 levels. Stromal cells in intestinal lymphoid follicles (LFs) are the predominant source of intestinal C3. During enteric infection withCitrobacter rodentiumor enterohemorrhagicEscherichia coli,luminal C3 levels increase significantly and are required for protection.C. rodentiumis remarkably more invasive to the gut epithelium of C3-deficient mice than of wild-type mice. In the gut, C3-mediated phagocytosis ofC. rodentiumfunctions to clear pathogens. Our study reveals that variations in gut microbiota determine individuals’ intestinal mucosal C3 levels, dominantly produced by LF stromal cells, which directly correlate with protection against enteric infection.HighlightsGut complement component 3 (C3) is induced by the microbiome in healthy humans and mice at a microbiota-specific level.Gut stromal cells located in intestinal lymphoid follicles are a major source of luminal C3During enteric infections withCitrobacter rodentiumor enterohemorrhagicEscherichia coli,gut luminal C3 levels increase and are required for protection.C. rodentiumis significantly more invasive of the gut epithelium in C3-deficient mice when compared to WT mice.In the gut, C3-mediated opsonophagocytosis ofC. rodentiumfunctions to clear pathogens.

Ultrahigh photoresponse with the record photoresponsivity is achieved by the strain- and domain-engineering of large-scale monolayer MoS2 films for maximum tensile strain and suitable atomic alignments.

The cellular function and structural configuration of the KEOPS complex have been elucidated in some eukaryotes and archaea but have never been fully characterized in fungal pathogens. Here, we comprehensively analyzed the pathobiological roles of the KEOPS complex in the globally prevalent fungal meningitis-causing pathogen C. neoformans .

BACKGROUND Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. OBJECTIVES The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. METHODS We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. RESULTS NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P

Purpose The current standard treatment for hypertrophic scars following burn injury is pressure garment therapy. The experimenters developed the novel portable pressure measuring device using silicon piezoresistive sensors. As PicoPress® is the most accurate (i.e., lowest variation and error) manometric sensor for pressure measurement, we sought to compare and examine the accuracy of the novel device regarding in vitro pressure measurements at the hypertrophic scar–pressure garment interface. Methods The novel device was designed to operate in non-corrosive media, such as air. The device can use up to six pressure sensing points and was developed to adjust the number of pressure sensors according to the size of the scar. Pressure measurements were acquired through a readout circuit consisting of an analog-to-digital converter, a microprocessor, and a Bluetooth transmission module for wireless data transmission to an external device. All signals were converted into mean pressure expressed in millimeters of mercury (mmHg). The mean pressure values measured by the sensors were compared to those obtained from PicoPress®. 55 garment pressures recordings were obtained from the sensors over this study conducted in 2018–February 2020. We then analyzed the test–retest reliability using the intraclass correlation coefficients (ICC). PicoPress® was also employed in the same pressure garments for obtaining similar measurements. A two way random effects model ICC with 95% confidence intervals was used to compare the mean pressure values obtained from the silicon piezoresistive sensors to the PicoPress® measurements. Results The test–retest reliability of the pressure sensors was close to the acceptable level for clinical use regarding stationary interface pressure measurement (ICC = 0.99, 95% CI 0.990−0.997). The mean pressure obtained from the silicon piezoresistive pressure sensors showed an accordance with the measurements from PicoPress® (ICC = 0.97, 95% CI 0.947−0.985). Conclusion The novel device may present a viable alternative to PicoPress® for garment pressure measurements. In addition, the novel device improves adaptability to the hypertrophic scar shape and size. Complementary characteristics such as wireless transmission to an external device may allow burn patients to continuously wear the device for real-time measurements during pressure garment therapy, thus improving existing devices including PicoPress®.

REM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson’s disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients unaffected by RBD (PD-RBD−). To elucidate this, we evaluated the availability of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in 15 PD patients with probable RBD (PD-RBD+), 15 PD-RBD−, and 15 age-matched healthy controls (HC) using [11C]DTBZ PET imaging. This technique measured VMAT2 availability within striatal regions of interest (ROI). A mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. We observed a significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, our results revealed that PD-RBD+ had lower VMAT2 availability compared to HC in all these regions except for the subthalamus and substantia nigra, while PD-RBD− was significantly lower than HC in all these regions. PD-RBD− showed a negative relationship between motor severity and VMAT2 availability within the left caudate. Our findings reflect that both PD patient subgroups had similar denervation within the nigrostriatal pathway. There were no significant interactions detected between radioligand binding and clinical scores in PD-RBD+. Taken together, VMAT2 and striatal dopamine denervation in general may not be a significant contributor to the pathophysiology of RBD in PD patients. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.

Patients undergoing maintenance hemodialysis (MHD) are susceptible to muscle wasting and decreased muscle function, resulting in shorter survival time. This study was aimed at evaluating the effect of radial extracorporeal shock wave therapy (rESWT) on muscle mass and function in patients on MHD. This single blind controlled study was conducted on patients on MHD from September 2018 to December 2019. Eighteen patients were enrolled in the rESWT and control groups. rESWT was performed once a week for 12 wk in both quadriceps femoris muscles of the ESWT group. Finally, 15 patients were assessed for body composition, handgrip strength, physical performance and blood chemistry before rESWT, after rESWT and at a 12-wk follow-up. Leg lean mass and appendicular skeletal muscle mass index increased significantly in the ESWT group compared with the control group (p = 0.001 and p = 0.017). The timed up-and-go test and sit-to-stand tests revealed greater significant improvement in the ESWT group (p = 0.023 and p = 0.046). This study is the first to report that rESWT can improve muscle mass and function in MHD patients. A subsequent study will be conducted to validate the clinical effects of rESWT in a larger sample of patients undergoing MHD.

Background An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. Methods MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. Results Of the 85 patients [age, 54.0 (41.0–65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65–148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02–1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08–1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. Conclusions The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

Objectives: Guided by the family systems theory (Bowen, 1966) and the Actor-Partner Interdependence Model (APIM; Cook & Kenny, 2005), this study examined the actor-partner effects of mother-adolescent communication on the psychological well-being of mothers and their adolescent children via mother-adolescent conflict and the differences between female and male adolescents.Methods: A total of 249 dyads of mothers and their adolescent children (age 13-16) in South Korea completed questionnaires on mother-adolescent communication, mother-adolescent conflict, and psychological well-being, respectively. The data were analyzed using Pearson’s correlation, path model analysis, and multiple group analysis.Results: First, the findings showed both partial actor and partner effects of perceived mother-adolescent communication on psychological well-being through a perceived level of conflict in both male and female adolescents and mother pairs. In addition, we examined sex differences for the aforementioned indirect pathways. There were sex differences in the indirect actor effects, in that mothers’ and adolescents’ own perceived communication had differential effects on psychological well-being indirectly through perceived conflict. The indirect partner effects also differed between male and female adolescents. The results of this study are meaningful because they emphasize the bidirectionality of the relationships among these variables.Conclusion: The findings contribute to the literature by highlighting the dyadic process in which mother-adolescent communication, conflict, and psychological well-being perceived by mothers and adolescents affect themselves as well as each other. This study is meaningful because the results emphasize the relationships between these variables. In utilizing a family systems approach, this study’s findings can aid in developing parent education programs, counseling interventions, and family policies that improve individuals’ psychological well-being.

The prevalence of atrial fibrillation (AF) is gradually increasing with the aging of the population, and there is also increasing interest in AF with the development of various single-lead electrocardiography measurement methods for diagnosis. Further, the current diagnosis and treatment policies for AF do not reflect its progression and complexity. In addition, the various factors related to AF diagnosis and treatment are not simple due to the diversification of tools, advances in treatment methods, and complex mechanism of AF. Therefore, there are many challenges to developing a simple AF classification system. To overcome these, there have been a number of attempts to systematically characterize AF according to treatment and prognosis rather than using a uniform classification. Further, as mentioned in the previous AF guidelines, further research is being conducted on an integrated patient-physician approach to AF. Such an approach would be the basis for consistent treatment based on the guidelines, and would help to improve patient outcomes. Further, for the integrated management of AF patients, some changes should be made to the current approach to develop a multidisciplinary approach, including changes to the behavior of team members, patients, their family members, and physicians. The Korean Heart Rhythm will introduce an integrated approach to the classification and structure of AF management, and provide guidelines for its application in clinical practice. (Korean J Med 2021;96:382-389)

OBJECTIVES We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING Multicenter ICU. PATIENTS Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Background: The lesion sets for surgical ablation of atrial fibrillation (AF) that provide optimal outcomes have remained controversial. Objectives: We evaluated the effects of left-atrial (LA) ablation of AF compared with bi-atrial (BA) ablation on the clinical and rhythm outcomes, and examined the predictors for AF recurrence and permanent pacing in consideration of ablation lesion sets. Methods: Between 2001 and 2018, 1,965 patients underwent surgical ablation during cardiac surgery at our institution. Among these, 796 and 1,169 patients underwent LA and BA ablation, respectively. The clinical outcomes were evaluated after propensity score adjustment, with death accounting for a competing event. The probability of AF recurrence was estimated with the generalized estimating equations model. Results: The patients with BA ablation had morbidities greater than those with LA ablation. The probability of AF recurrence at 1 and 5 years was 13.9% and 37.1% in patients with LA ablation, and 11.2% and 30.1% in those with BA ablation (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 0.96-1.61; P = 0.100). After adjustment, LA ablation was associated with a decreased risk of early death (