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Genetic variants in Ankyrin Repeat Domain 11 (ANKRD11) and deletions in 16q24.3 are known to cause KBG syndrome, a rare syndrome associated with craniofacial, intellectual, and neurobehavioral anomalies. We report 25 unpublished individuals from 22 families with molecularly confirmed diagnoses. Twelve individuals have de novo variants, three have inherited variants, and one is inherited from a parent with low-level mosaicism. The mode of inheritance was unknown for nine individuals. Twenty are truncating variants, and the remaining five are missense (three of which are found in one family). We present a protocol emphasizing the use of videoconference and artificial intelligence (AI) in collecting and analyzing data for this rare syndrome. A single clinician interviewed 25 individuals throughout eight countries. Participants’ medical records were reviewed, and data was uploaded to the Human Disease Gene website using Human Phenotype Ontology (HPO) terms. Photos of the participants were analyzed by the GestaltMatcher and DeepGestalt, Face2Gene platform (FDNA Inc, USA) algorithms. Within our cohort, common traits included short stature, macrodontia, anteverted nares, wide nasal bridge, wide nasal base, thick eyebrows, synophrys and hypertelorism. Behavioral issues and global developmental delays were widely present. Neurologic abnormalities including seizures and/or EEG abnormalities were common (44%), suggesting that early detection and seizure prophylaxis could be an important point of intervention. Almost a quarter (24%) were diagnosed with attention deficit hyperactivity disorder and 28% were diagnosed with autism spectrum disorder. Based on the data, we provide a set of recommendations regarding diagnostic and treatment approaches for KBG syndrome.

A thickened peroneus brevis tendon has been considered to be an important morphologic parameter of peroneus brevis tendinitis (PBT). Previous researchers have found that the peroneus brevis tendon thickness (PBTT) is correlated with inflammation of the peroneus brevis tendon. However, inflammatory hypertrophic change is different from simple thickness. Thus, we devised the peroneus brevis tendon cross-sectional area (PBTCSA) as a new diagnostic parameter to analyze the hypertrophy of the whole PBT. We assumed that the PBTCSA is a major morphologic parameter useful for early PBT diagnosis. Peroneus brevis tendon images were collected from 22 patients with PBT and from 22 normal subjects who underwent ankle-magnetic resonance imaging and revealed no evidence of PBT. The T1-weighted axial ankle-magnetic resonance imaging images were evaluated at the ankle level from all participants. The PBTT was measured as the thickest point at the transverse image of the peroneus brevis tendon. The PBTCSA was measured as the cross-sectional ligament whole area of the peroneus brevis tendon that was most hypertrophied in the axial A-MR images. The average PBTT was 2.22 ± 0.29 mm in the normal group and 2.85 ± 0.36 mm in the PBT group. The average PBTCSA was 6.98 ± 1.54 mm2 in the normal group and 13.11 ± 2.45 mm2 in the PBT group. PBT patients had significantly greater PBTT (P.001) and PBTCSA (P.001) than the normal group did. A receiver operating characteristic curve analysis revealed that the most suitable cutoff value of the PBTT was 2.51 mm, with 81.8% sensitivity and 81.8% specificity, and an AUC for the score was 0.93. The most suitable cutoff value of the PBTCSA was 10.08 mm2, with 90.9% sensitivity and 90.9% specificity, and AUC for the score was 0.98. Even though the PBTT and PBTCSA were both significantly associated with PBT, the PBTCSA was a more sensitive diagnostic parameter.

The Korean Knee Society (KKS) score is used for functional evaluation during follow-up after total knee arthroplasty (TKA), but it is time-consuming to measure and is limited by its subjective nature. We investigated whether the global gait asymmetry index (GGA) that can be obtained using the Kinect-V2 system could overcome the KKS limitations.Forty-three patients who underwent TKA from January 2019 to December 2019 were included. Postoperatively, regular follow-up was performed at 2, 4, 6, 8, and 12 weeks, and at 4, 6, and 12 months. At each follow-up visit, the KKS was measured, and the walking path was followed with six Kinect-V2 systems. After allowing the participants to walk naturally, the range of motion of each joint of the lower extremity and GGA were obtained. Changes in the KKS and GGA scores and measurement times were investigated until the final follow-up. A statistical model was made to predict the KKS from the GGA score using data at all observed time points, and analysis of variance (ANOVA) with Turkey's post-hoc tests and Pearson correlation tests were used for evaluation.Both the KKS and GGA scores improved significantly from 4 weeks postoperatively until the final follow-up. The measurement time was significantly shorter for the GGA (9.3 ± 1.4 min) than for the KKS (32.4 ± 9.2 min; P 0.001) score. The predicted and actual KKS values clustered close to a straight line on the scatter plot, but the prediction was less accurate in the initial stage (2 weeks post-surgery) than at later time points. The mean absolute error (MAE) and root mean square of the error (RMSE) were considered to be poorly predicted in the initial stage (8 weeks post-surgery) compared to the later time-points (MAE ≥ 5 and RMSE ≥ 6 for 8 weeks post-surgery).In the early phase after knee joint surgery (up to 12 weeks post-surgery), the GGA index does not predict the KKS well. However, after this time point, the GGA index can be simply measured in the outpatient department and may be able to replace the KKS. Thus, evaluation of the GGA index using the Kinect-V2 may be a useful method to evaluate functional recovery in the outpatient clinic after knee joint surgery.

Many heterologous proteins can be secreted by bacterial ATP-binding cassette (ABC) transporters, provided that they are fused with the C-terminal signal sequence, but some proteins are not secretable even though they carry the right signal sequence. The invention of a method to secrete these non-secretable proteins would be valuable both for understanding the secretory physiology of ABC transporters and for industrial applications. Herein, we postulate that cationic “supercharged” regions within the target substrate protein block the secretion by ABC transporters. We also suggest that the secretion of such substrate proteins can be rescued by neutralizing those cationic supercharged regions via structure-preserving point mutageneses. Surface-protruding, non-structural cationic amino acids within the cationic supercharged regions were replaced by anionic or neutral hydrophilic amino acids, reducing the cationic charge density. The examples of rescued secretions we provide include the spike protein of SARS-CoV-2, glutathione-S-transferase, streptavidin, lipase, tyrosinase, cutinase, growth factors, etc. In summary, our study provides a method to predict the secretability and a tool to rescue the secretion by correcting the secretion-blocking regions, making a significant step in understanding the physiological properties of ABC transporter-dependent protein secretion and laying the foundation for the development of a secretion-based protein-producing platform.

Previous studies have demonstrated that morphological changes in the suprascapular notch are closely associated with suprascapular nerve entrapment syndrome (SNES). Thus, we hypothesized that the suprascapular notch cross-sectional area (SSNCSA) could be a good diagnostic parameter to assess SNES.We acquired suprascapular notch data from 10 patients with SNES and 10 healthy individuals who had undergone shoulder magnetic resonance imaging (S-MRI) and had no evidence of SNES. T2-weighted coronal magnetic resonance images were acquired from the shoulder. We analyzed the SSNCSA at the shoulder on S-MRI using our image-analysis program (INFINITT PACS). The SSNCSA was measured as the suprascapular notch, which was the most affected site in coronal S-MRI images.The mean SSNCSA was 64.50 ± 8.93 mm2 in the control group and 44.94 ± 10.40 mm2 in the SNES group. Patients with SNES had significantly lower SSNCSA (P0.01) than those in the control group. Receiver operating curve analysis showed that the best cut-off of the SSNCSA was 57.49 mm2, with 80.0% sensitivity, 80.0% specificity, and an area under the curve of 0.92 (95% CI [0.79, 1.00]).The SSNCSA was found to have acceptable diagnostic properties for detecting SNES. We hope that these results will help diagnose SNES objectively.

The generation of a mesoporous structure in platinum nanoparticles can effectively enhance physical and chemical properties. In this study, mesoporous platinum nanoparticles (MPNs) were synthesized by a soft template-mediated one-pot chemical method. To develop a mesoporous structure, Pluronic F-127 was employed. The Pluronic F-127 surfactant forms self-assembled micelles, and the micelles act as the pore-directing agents in the synthesis of nanoparticles. Scanning electron microscopy results revealed that the MPN had a uniform size of 70 nm on average and a distinct mesoporous structure. The development of a concave mesoporous structure on the surface of the MPNs can increase the surface area and facilitate the efficient transport of reactants. The synthesized MPNs exhibited peroxidase-like activity. Furthermore, the MPNs showed excellent catalytic efficiency compared to HRP, due to the high surface area derived from the presence of the mesoporous structure. The peroxidase-like MPNs were applied to the enzyme-linked immunosorbent assay (ELISA) of C-reactive protein (CRP). The MPN-based ELISA exhibited sensitive CRP detection in the range from 0.24 to 7.8 ng/mL with a detection limit of 0.13 ng/mL. Moreover, the recoveries of the CRP concentrations in spiked human serum were 98.6% and 102%. These results demonstrate that as a peroxidase mimic, the MPNs can replace the natural enzymes in conventional ELISA for sensitive CRP detection.

Whether subjects with NAFLD are at increased risk of sarcopenia is not well established.This is a cohort study of 52,815 men and women of 20 years of age or older who underwent at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging. Bioelectrical impedance analysis was used to calculate appendicular skeletal muscle mass (ASM). NAFLD was assessed by ultrasonography, and its severity was assessed by the NAFLD fibrosis score (NFS). We estimated the 5-year change in ASM comparing participants with and without NAFLD at baseline using mixed linear models. The 5-year change in ASM in participants without and with NAFLD was -225.2 g (95% CI -232.3, -218.0) and -281.3 g (95% CI -292.0, -270.6), respectively (p 0.001). In multivariable adjusted analysis, the difference in 5-year change in ASM comparing participants with and without NAFLD was -39.9 g (95% CI -53.1, -26.8). When participants with NAFLD were further divided by NAFLD severity, ASM loss was much faster in participants with NAFLD with intermediate to high NFS than in those with low NFS.Participants with NAFLD were at increased risk of sarcopenia, indicated by faster loss of skeletal muscle mass. Patients with NAFLD may need screening and early intervention to mitigate skeletal muscle mass loss.

Background Arterial cannulation in elderly patients is difficult because of age-related morphological changes. Applying dynamic needle tip positioning (DNTP) that guides the catheter to position inside the vessel sufficiently may aid in successful cannulation. Methods This prospective study enrolled patients aged over 70 years, who were scheduled for elective surgery under general anaesthesia with arterial cannulation. The patients were randomly assigned to the DNTP (group D, n = 76) or the conventional short-axis view(group C, n = 75) group. The arterial depth, diameter, and arterial conditions(calcification, segmental stenosis, and tortuosity) were evaluated using ultrasound, before puncture. We recorded the first attempt success, cannulation time, the number of attempts, and cannulation-related complications. Results A total of 151 patients were enrolled in this study. The first attempt success rate in group D was significantly higher than that in group C (89% versus 72%; P = 0.0168). The median cannulation time per last attempt in group D versus group C was 25 versus 30 sec(P = 0.0001), and the overall cannulation time was 25 versus 35 sec(P = 0.0001), respectively. Arterial cannulation per last attempt and overall cannulation time were shorter in group D. The number of attempts was higher in group C (P = 0.0038). The occurrence rate of hematoma was significantly lower in group D (16% versus 47%, relative risk = 3.0, P = 0.0001). Conclusions The DNTP method may improve the first attempt success rate of arterial cannulation and reduce complications in elderly patients over 70 years of age.

The usefulness of the oxygen reserve index (ORi) in reducing hyperoxemia remains unclear. We designed this study to investigate whether fraction of inspired oxygen (FiO2) adjustment under a combination of ORi and peripheral oxygen saturation (SpO2) guidance can reduce intraoperative hyperoxemia compared to SpO2 alone.In this prospective, double-blind, randomized controlled study, we allocated patients scheduled for laparoscopic gastrectomy to the SpO2 group (FiO2 adjusted to target SpO2 ≥ 98%) or the ORi-SpO2 group (FiO2 adjusted to target 00 ORi.3 and SpO2 ≥ 98%). The ORi, SpO2, FiO2, arterial partial pressure of oxygen (PaO2), and incidence of severe hyperoxemia (PaO2 ≥ 200 mm Hg) were recorded before and 1, 2, and 3 hours after surgical incision. Data from 32 and 30 subjects in the SpO2 and ORi-SpO2 groups, respectively, were analyzed.PaO2 was higher in the SpO2 group (250.31 ± 57.39 mm Hg) than in the ORi-SpO2 group (170.07 ± 49.39 mm Hg) 1 hour after incision (P.001). PaO2 was consistently higher in the SpO2 group than in the ORi-SpO2 group, over time (P = .045). The incidence of severe hyperoxemia was higher in the SpO2 group (84.4%) than in the ORi-SpO2 group (16.7%, P.001) 1 hour after incision. Higher FiO2 was administered to the SpO2 group [52.5 (50-60)] than the ORi-SpO2 group [40 (35-50), P.001] 1 hour after incision. SpO2 was not different between the 2 groups.The combination of ORi and SpO2 guided FiO2 adjustment reduced hyperoxemia compared to SpO2 alone during laparoscopic gastrectomy.

Despite growing evidence of the relevance of alternative splicing (AS) to cancer development and progression, the biological implications of AS for tumor behaviors, including papillary thyroid cancer (PTC), remain elusive. With the aim of further understanding the molecular and histological subtypes of PTC, we in this study explored whether AS events might act as new molecular determinants. For this purpose, AS profiles were analyzed in RNA-sequencing data from The Cancer Genome Atlas (TCGA) and from a Korean patient dataset. A total of 23 distinct exon-skipping (ES) events that correlated significantly with PTC oncogenic activity and differentiation scores were identified. The two top-ranked ES events, NUMA1_17515 in exon 18 of NUMA1 and TUBB3_38175 in exon 6 of TUBB3, showed high correlations with oncogenic activities and discriminated histological and molecular subtypes of PTC. Furthermore, two novel intron-retention (IR) events for TUBB3 were uncovered. All ES and IR events for the TUBB3 gene were predicted to induce nonsense-mediated mRNA decay. The relative abundances of intron reads in the PTC dataset from TCGA showed IR levels to differ significantly among PTC subtypes, possibly reflecting their different tumor behaviors. This study provides a landscape of AS changes among PTC subtypes and identified two significant AS events, NUMA1_17515 and TUBB3_38175, as potential AS biomarkers for PTC subclassification and characterization. The AS events identified in this study may be involved in the development of phenotypic differences underlying the functional characteristics and histological differentiation of PTCs.

Background Since the femoral artery frequently overlaps the femoral vein, femoral central venous catheterization carries the risk of arterial puncture in pediatric patients. Aims We evaluated the angle range of leg abduction with external hip rotation to minimize the overlap between the femoral artery and vein in pediatric patients undergoing general anesthesia. Methods Eighty-two pediatric patients who underwent elective surgery with general anesthesia were enrolled in this study. Using ultrasonography, patients were divided into groups N (patients with non-overlap) and O (patients with continuing overlap) based on the presence of non-overlap range between the femoral artery and vein. The range minimizing the overlap was defined as the range without overlap in group N and as the range presenting the overlap that was less-than-half of the radius of the femoral vein in group O. By increasing the angle of leg abduction with external hip rotation, the starting and ending angles minimizing the overlap were found using ultrasonographic images. Results The angle range of leg abduction with external hip rotation minimizing the overlap between the femoral artery and vein was defined as the range from the maximum 99% confidence interval of starting angles to the minimum 99% confidence interval of ending angles, which was between 45° and 65° in group N and between 48° and 58° in group O, respectively. Conclusion Positioning patients in a range of 48° and 58° leg abduction with external hip rotation can minimize the overlap between the femoral artery and vein. However, the clinical usefulness of this positioning for femoral venous catheterization remains to be seen.

Ultrasound is not widely used to evaluate optimal supraglottic airway positioning even though it could potentially be used to identify and correct problem areas.We evaluated a new ultrasound scoring method to identify the position of the supraglottic airway and detect the location of air leaks during ventilation in pediatric patients.Using a prospective observational study design, we enrolled 90 pediatric patients of ASA physical status I-III scheduled for elective surgery under general anesthesia. After anesthesia induction, patients were assigned to a noncorrection group or a correction group after their first ultrasound evaluation. Noncorrection group comprised patients with tolerable I-Gel positioning based on ultrasound evaluation and no problems with clinical parameters, while the correction group comprised patients with I-Gel mispositioning based on ultrasound.After the first ultrasound evaluation, 61 patients did not need I-Gel correction (noncorrection group), while 29 patients needed I-Gel correction (correction group) and underwent a second ultrasound evaluation. Airway sealing pressure and total ultrasound score showed a negative correlation (r = -.845, p .001). The area under the receiver operating curve for total ultrasound score was 0.97 (95% confidence interval, 0.94-0.99; p .001). In the correction group, ultrasound score and ventilation parameters improved after correction based on ultrasound evaluation.Ultrasound scores were negatively correlated with airway sealing pressure in pediatric patients. Ultrasound evaluation is useful for detecting misplacement of the I-Gel and can be a useful tool for correction.

Virtual manipulatives are interactive and dynamic visual objects on a screen, which allow students to manipulate them to construct mathematical knowledge. The purpose of this study was to synthesize the literature on interventions that used virtual manipulatives to improve the mathematics performance of K–12 students with learning disabilities. A total of 19 single-case design studies (16 peer-reviewed articles and three dissertations) were selected using specific selection criteria. Overall, students with learning disabilities demonstrated mathematical improvement after receiving interventions involving virtual manipulatives. Although many students with learning disabilities maintained and generalized the intervention effects, further research is required to verify the current findings.

This study investigated the abundance and diversity of antibiotic resistance genes (ARGs) and the composition of bacterial communities along a transect covering the western Pacific Ocean (36°N) to the Southern Ocean (74°S) using the Korean icebreaker R/V Araon (total cruise distance: 14,942 km). The relative abundances of ARGs and bacteria were assessed with quantitative PCR and next generation sequencing, respectively. The absolute abundance of ARGs was 3.0 × 10

In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.

FMS-like receptor tyrosine kinase-3 (FLT3) is expressed on acute leukemia cells and is implicated in the survival, proliferation and differentiation of hematopoietic cells in most acute myeloid leukemia (AML) patients. Despite recent achievements in the development of FLT3-targeted small-molecule drugs, there are still unmet medical needs related to kinase selectivity and the progression of some mutant forms of FLT3. Herein, we describe the discovery of novel orally available type 1 FLT3 inhibitors from structure-activity relationship (SAR) studies for the optimization of indirubin derivatives with biological and pharmacokinetic profiles as potential therapeutic agents for AML. The SAR exploration provided important structural insights into the key substituents for potent inhibitory activities of FLT3 and in MV4-11 cells. The profile of the most optimized inhibitor (36) showed IC50 values of 0.87 and 0.32 nM against FLT3 and FLT3/D835Y, respectively, along with potent inhibition against MV4-11 and FLT3/D835Y expressed MOLM14 cells with a GI50 value of 1.0 and 1.87 nM, respectively. With the high oral bioavailability of 42.6%, compound 36 displayed significant in vivo antitumor activity by oral administration of 20 mg/kg once daily dosing schedule for 21 days in a mouse xenograft model. The molecular docking study of 36 in the homology model of the DFG-in conformation of FLT3 resulted in a reasonable binding mode in type 1 kinases similar to the reported type 1 FLT3 inhibitors Crenolanib and Gilteritinib.

Carrageenan (CGN), a widely used food additive, has been shown to injure the epithelial barrier in animal models. This type of damage is a clinical feature of inflammatory bowel disease (IBD) in humans. In the present study, the effects of CGN on pro-apoptotic responses associated with macrophage inhibitory cytokine 1 (MIC-1) regulation in human enterocytes were evaluated. CGN up-regulated the expression of MIC-1 that promoted epithelial cell apoptosis. Although MIC-1 induction was dependent on pro-apoptotic p53 protein, the pro-survival protein activating transcription factor 3 (ATF3) was negatively regulated by p53 expression. However, MIC-1 enhanced the expression of the pro-survival protein ATF3 in enterocytes exposed to CGN. Functionally, MIC-1-mediated epithelial cell apoptosis was counteracted by the pro-survival action of ATF3 in response to CGN exposure. These findings demonstrated that the counterbalance between MIC-1 and ATF3 is critical for deciding the fate of enterocytes under the food chemical stress.

Direct self-injurious behaviour (D-SIB) is associated with suicidal behaviour and suicide risk. It is not known if D-SIB cessation reduces these risks. The aim of this study was to explore trajectories of D-SIB and their prospective influence on suicidal thoughts and behaviour during adolescence. Data (n = 506; 62.06 % females, 14.53 years) from the Saving and Empowering Young Lives in Europe study were analysed. D-SIB and suicidal thoughts and behaviour were assessed at baseline (T0), 1- (T1) and 2-year follow-up (T2). Onset and maintenance of D-SIB between T0 and T1 were associated with a two to threefold increased odds ratio for suicidal thoughts and behaviour at T2. Suicidal thoughts and behaviour in those terminating D-SIB before T1 were similar compared to those with no life-time history of D-SIB. Late onset and maintenance of D-SIB prospectively indicate risk for suicidal thoughts and behaviour. This is the first study showing that D-SIB cessation reduces later risk for suicidal thoughts and behaviour in adolescence. Suicide prevention efforts should set one focus on reducing adolescent D-SIB.

Although social skills training (SST) is an effective approach for improving social skills for schizophrenia, the motivational deficit attenuates its efficacy. Virtual reality (VR) applications have allowed individuals with mental disabilities to enhance their motivation for rehabilitation. We compared SST using VR role-playing (SST-VR) to SST using traditional role-playing (SST-TR). This randomized, controlled trial included 91 inpatients with schizophrenia who were assigned to either SST-VR (n=46) or SST-TR (n=45). Both groups were administered over 10 semiweekly group sessions. An experienced, blinded rater assessed vocal, nonverbal and conversational skills. We also obtained data on motivation for SST and various social abilities. Throughout the 10 sessions, the SST-VR group (n=33) showed greater interest in SST and generalization of the skills than the SST-TR group (n=31). After SST, the SST-VR group improved more in conversational skills and assertiveness than the SST-TR group, but less in nonverbal skills. The VR application in role-plays of SST for schizophrenia may be particularly beneficial in terms of improving the conversational skills and assertiveness, possibly through its advantages in enhancing motivation for SST and generalization of the skills, and thus it may be a useful supplement to traditional SST.

Objective The objective of this study was to explore the possibility of the use of Virtual Reality Functional Skills Assessment (VRFSA) in a future regular clinical trial, as well as to report a preliminary result about effectiveness of atypical antipsychotics to social competence in schizophrenia. Methods We developed the VRFSA that measured subjects' performances automatically and used analogue scale rather than Likert scale. Twenty-four female patients with paranoid schizophrenia and 15 healthy females were recruited. This was a 6-week, randomized, open-label, and flexible dose study, and 2 treatments (baseline versus post-treatment) × 2 skills phases (receptive versus expressive) × 2 patient groups (aripiprazole versus risperidone) analysis of variance was used in the final analysis. Results There was a significant difference in the VRFAS between the patients and the healthy subjects (p

There is still debate over the neural mechanisms underlying pathogenic and even recovery processes of Wernicke's encephalopathy. Therefore, we attempted to validate the usefulness of resting-state functional connectivity analysis in assessing memory function and its neural correlation with the mammillothalamic tract in patients recovering from Wernicke's encephalopathy. Seven chronic alcoholics recovering from Wernicke's encephalopathy, 14 alcoholic comparisons without Wernicke's encephalopathy, and 14 healthy comparisons underwent functional connectivity MRI scans, as well as verbal and non-verbal memory tests after at least a 1 month abstinence from alcohol. Resting-state functional connectivity strength between the anterior thalamus and the mammillary bodies was investigated by calculating temporal correlations in magnetic resonance signal levels between the two regions during a 5-min passive viewing task. The mean values of the functional connectivity strength between the left anterior thalamus and the ipsilateral mammillary body differed significantly between Wernicke's encephalopathy patients and healthy comparisons (P = 0.014). This connectivity strength in alcoholic comparisons fell between those of the former two groups, with a significant difference from that of healthy comparisons (P = 0.038). In addition, the strength of this left-sided functional connectivity significantly correlated with delayed verbal recall scores (r = 0.771, P = 0.042) and verbal recognition score (r = 0.825, P = 0.022) in patients with Wernicke's encephalopathy. Our findings indicate that memory function in patients recovering from Wernicke's encephalopathy parallels the level of the mammillothalamic functional connectivity; this supports the usefulness of resting-state functional connectivity analysis as a practical alternative to pathological examination of the mammillothalamic tract in living patients with Wernicke's encephalopathy.

In this qualitative inquiry we investigated the conceptualization of family quality of life. Focus groups and individual interviews were conducted with 187 individuals: family members (e.g., parents, siblings) of children with a disability, individuals with a disability, family of children without a disability, service providers, and administrators. Data were collected in urban and rural settings to elicit the participants' understanding of family quality of life. Ten domains of family quality of life were identified and described in terms of subdomains, indicators, and key points raised by participants. Implications are discussed in terms of future directions for research and family support.

In response to excessive nucleotide-binding oligomerization domain–containing protein 2 (Nod2) stimulation caused by mucosal bacterial components, gut epithelia need to activate regulatory machinery to maintain epithelial homeostasis. Activating transcription factor 3 (ATF3) is a representative regulator in the negative feedback loop that modulates TLR-associated inflammatory responses. In the current study, the regulatory effects of ribosomal stress-induced ATF3 on Nod2-stimulated proinflammatory signals were assessed. Ribosomal inactivation caused persistent ATF3 expression that in turn suppressed proinflammatory chemokine production facilitated by Nod2. Decreased chemokine production was due to attenuation of Nod2-activated NF-κB and early growth response protein 1 (EGR-1) signals by ATF3. However, the underlying molecular mechanisms involve two convergent regulatory pathways. Although ATF3 induced by ribosomal inactivation regulated Nod2-induced EGR-1 expression epigenetically through the recruitment of histone deacetylase 1, NF-κB regulation was associated with posttranscriptional regulation by ATF3 rather than epigenetic modification. ATF3 induced by ribosomal inactivation led to the destabilization of p65 mRNA caused by nuclear entrapment of transcript-stabilizing human Ag R protein via direct interaction with ATF3. These findings demonstrate that ribosomal stress-induced ATF3 is a critical regulator in the convergent pathways between EGR-1 and NF-κB, which contributes to the suppression of Nod2-activated proinflammatory gene expression.

Background The concept of family quality of life (QoL) has emerged as an important outcome of service delivery for individuals with disabilities and their families. The present study describes the process of developing a tool to measure family QoL. Methods and Results A total of 1197 respondents participated in a national field test. Through factor analysis, the survey was refined in several ways: (1) the preliminary 10-domain structure was reduced to a five-domain structure; (2) a total of 41 items were selected for the revised survey; and (3) wordings were clarified. Conclusions The implications for future research and practice are discussed.