Atypical Integration of Sensory-to-Transmodal Functional Systems Mediates Symptom Severity in Autism.

A notable characteristic of autism spectrum disorder (ASD) is co-occurring deficits in low-level sensory processing and high-order social interaction. While there is evidence indicating detrimental cascading effects of sensory anomalies on the high-order cognitive functions in ASD, the exact pathological mechanism underlying their atypical functional interaction across the cortical hierarchy has not been systematically investigated. To address this gap, here we assessed the functional organisation of sensory and motor areas in ASD, and their relationship with subcortical and high-order trandmodal systems. In a resting-state fMRI data of 107 ASD and 113 neurotypical individuals, we applied advanced connectopic mapping to probe functional organization of primary sensory/motor areas, together with targeted seed-based intrinsic functional connectivity (iFC) analyses. In ASD, the connectopic mapping revealed topological anomalies (i.e., excessively more segregated iFC) in the motor and visual areas, the former of which patterns showed association with the symptom severity of restricted and repetitive behaviors. Moreover, the seed-based analysis found diverging patterns of ASD-related connectopathies: decreased iFCs within the sensory/motor areas but increased iFCs between sensory and subcortical structures. While decreased iFCs were also found within the higher-order functional systems, the overall proportion of this anomaly tends to increase along the level of cortical hierarchy, suggesting more dysconnectivity in the higher-order functional networks. Finally, we demonstrated that the association between low-level sensory/motor iFCs and clinical symptoms in ASD was mediated by the high-order transmodal systems, suggesting pathogenic functional interactions along the cortical hierarchy. Findings were largely replicated in the independent dataset. These results highlight that atypical integration of sensory-to-high-order systems contributes to the complex ASD symptomatology

Should HLA-B*5701 Screening Be Performed in Every Ethnic Group before Starting Abacavir?

Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans.Saag M, 2008, CLIN INFECT DIS, V46, P1111, DOI 10.1086/529382Mallal S, 2008, NEW ENGL J MED, V358, P568*PAN ANT GUID AD A, 2008, GUID US ANT AG HIV 1Waters LJ, 2007, AIDS, V21, P2533Sun HY, 2007, J ANTIMICROB CHEMOTH, V60, P599, DOI 10.1093/jac/dkm243Rauch A, 2006, CLIN INFECT DIS, V43, P99Phillips EJ, 2006, CLIN INFECT DIS, V43, P103Martin AM, 2005, TISSUE ANTIGENS, V65, P571, DOI 10.1111/j.1399-0039.2005.00401.xLee KW, 2005, TISSUE ANTIGENS, V65, P437, DOI 10.1111/j.1399-0039.2005.00386.xMiddleton D, 2004, TISSUE ANTIGENS, V63, P555Phillips EJ, 2002, AIDS, V16, P2223Saito S, 2000, TISSUE ANTIGENS, V56, P522Park MH, 1999, TISSUE ANTIGENS, V53, P3861

Clinical Features, Risk Factors and Outcomes of Bacteremia due to Enterococci with High-Level Gentamicin Resistance: Comparison with Bacteremia due to Enterococci without High-Level Gentamicin Resistance

High-level gentamicin resistance (HLGR) in enterococci has increased since the 1980s, but the clinical significance of the resistance and its impact on outcome have not been established. One hundred and thirty-six patients with bacteremia caused by enterococci with HLGR (HLGR group) were compared with 79 patients with bacteremia caused by enterococci without HLGR (non-HLGR group). Hematologic malignancy, neutropenia, Enterococcus faecium infection, nosocomial infection and monomicrobial bacteremia were more common in the HLGR group than the non-HLGR group, and APACHE II scores were also higher (P<0.05, in each case). Neutropenia, monomicrobial infection, stay in intensive care at culture, and use of 3rd generation cephalosporin, were independent risk factors for acquisition of HLGR enterococcal bacteremia. Fourteen-day and 30-day mortalities were higher in the HLGR group than the non-HLGR group in univariate analysis (37% vs. 15%, P=0.001; 50% vs. 22%, P<0.001). However, HLGR was not an independent risk factor for mortality due to enterococcal bacteremia in multivariate analysis. Therefore, HLGR enterococcal bacteremia is associated with more severe comorbid conditions and higher mortality than non-HLGR enterococcal bacteremia but the HLGR itself does not contribute significantly to mortality

Salvage Treatment for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Efficacy of Linezolid With or Without Carbapenem

Background. Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high mortality rates, but no treatment strategy has yet been established. We performed this study to evaluate the efficacy of linezolid with or without carbapenem in salvage treatment for persistent MRSA bacteremia. Methods. All adult patients with persistent MRSA bacteremia for >= 7 days from January 2006 through March 2008 who were treated at Seoul National University Hospital were studied. The results of linezolid salvage therapy with or without carbapenem were compared with those of salvage therapy with vancomycin plus aminoglycosides or rifampicin. Results. Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs 17%; P = .006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate (P < .001). The S. aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs 53%; P = .030). Conclusions. Linezolid-based salvage therapy effectively eradicated S. aureus from the blood for patients with persistent MRSA bacteremia. The salvage success rate was higher for linezolid therapy than for vancomycin-based combination therapy.Jenkins TC, 2008, CLIN INFECT DIS, V46, P1000, DOI 10.1086/529190Falagas ME, 2008, LANCET INFECT DIS, V8, P53, DOI 10.1016/S1473-3099(07)70312-2Hawkins C, 2007, ARCH INTERN MED, V167, P1861Kollef MH, 2007, CLIN INFECT DIS, V45, pS191, DOI 10.1086/519470Micek ST, 2007, CLIN INFECT DIS, V45, pS184, DOI 10.1086/519471*CLIN LAB STAND I, 2007, M100S17 CLIN LAB STAHidayat LK, 2006, ARCH INTERN MED, V166, P2138Howden BP, 2006, ANTIMICROB AGENTS CH, V50, P3039, DOI 10.1128/AAC.00422-06Hageman JC, 2006, CLIN INFECT DIS, V43, pE42Jacqueline C, 2006, ANTIMICROB AGENTS CH, V50, P2547, DOI 10.1128/AAC.01501-05Sakoulas G, 2006, CLIN INFECT DIS, V42, pS40Jones RN, 2006, CLIN INFECT DIS, V42, pS13Khatib R, 2006, SCAND J INFECT DIS, V38, P7, DOI 10.1080/00365540500372846Wu VC, 2006, CLIN INFECT DIS, V42, P66Jacqueline C, 2005, ANTIMICROB AGENTS CH, V49, P45, DOI 10.1128/AAC.49.1.45-51.2005*CDCP, 2005, CA MRSA CLIN FAQS CDFowler VG, 2004, J INFECT DIS, V190, P1140Wisplinghoff H, 2004, CLIN INFECT DIS, V39, P309, DOI 10.1086/421946Khosrovaneh A, 2004, CLIN INFECT DIS, V38, P1328Howden BP, 2004, CLIN INFECT DIS, V38, P521KIM SH, 2004, 42 ANN M INF DIS SOC, P142Fowler VG, 2003, ARCH INTERN MED, V163, P2066Kim SH, 2003, CLIN INFECT DIS, V37, P794Moise PA, 2002, J ANTIMICROB CHEMOTH, V50, P1017, DOI 10.1093/jac/dkf215Li JS, 2000, CLIN INFECT DIS, V30, P633You I, 2000, DIAGN MICR INFEC DIS, V36, P37Lowy FD, 1998, NEW ENGL J MED, V339, P520Hiramatsu K, 1997, LANCET, V350, P1670LIBMAN H, 1984, ARCH INTERN MED, V144, P5411

GSK3B induces autophagy by phosphorylating ULK1

Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian homolog of the yeast kinase Atg1, has an essential role in autophagy induction. In nutrient and growth factor signaling, ULK1 activity is regulated by various posttranslational modifications, including phosphorylation, acetylation, and ubiquitination. We previously identified glycogen synthase kinase 3 beta (GSK3B) as an upstream regulator of insulin withdrawal-induced autophagy in adult hippocampal neural stem cells. Here, we report that following insulin withdrawal, GSK3B directly interacted with and activated ULK1 via phosphorylation of S405 and S415 within the GABARAP-interacting region. Phosphorylation of these residues facilitated the interaction of ULK1 with MAP1LC3B and GABARAPL1, while phosphorylation-defective mutants of ULK1 failed to do so and could not induce autophagy flux. Furthermore, high phosphorylation levels of ULK1 at S405 and S415 were observed in human pancreatic cancer cell lines, all of which are known to exhibit high levels of autophagy. Our results reveal the importance of GSK3B-mediated phosphorylation for ULK1 regulation and autophagy induction and potentially for tumorigenesis. © 2021, The Author(s).1

Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition

Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut&#8315;brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration

Risk Assessment Method Combining Independent Protection Layers (IPL) of Layer of Protection Analysis (LOPA) and RISKCURVES Software: Case Study of Hydrogen Refueling Stations in Urban Areas

The commercialization of eco-friendly hydrogen vehicles has elicited attempts to expand hydrogen refueling stations in urban areas; however, safety measures to reduce the risk of jet fires have not been established. The RISKCURVES software was used to evaluate the individual and societal risks of hydrogen refueling stations in urban areas, and the F–N (Frequency–Number of fatalities) curve was used to compare whether the safety measures satisfied international standards. From the results of the analysis, it was found that there is a risk of explosion in the expansion of hydrogen refueling stations in urban areas, and safety measures should be considered. To lower the risk of hydrogen refueling stations, this study applied the passive and active independent protection layers (IPLs) of LOPA (Layer of Protection Analysis) and confirmed that these measures significantly reduced societal risk as well as individual risk and met international standards. In particular, such measures could effectively reduce the impact of jet fire in dispensers and tube trailers that had a high risk. Measures employing both IPL types were efficient in meeting international standard criteria; however, passive IPLs were found to have a greater risk reduction effect than active IPLs. The combination of RISKCURVES and LOPA is an appropriate risk assessment method that can reduce work time and mitigate risks through protective measures compared to existing risk assessment methods. This method can be applied to risk assessment and risk mitigation not only for hydrogen facilities, but also for hazardous materials with high fire or explosion risk

Real-Time Determination of Relative Position Between Satellites Using Laser Ranging

We made a study on real-time determination method for relative position using the laser-measured distance data between satellites. We numerically performed the determination of relative position in accordance with extended Kalman filter algorithm using the vectors obtained through nonlinear equation of relative motion, laser simulator for distance measurement, and attitude determination of chief satellite. Because the spherical parameters of relative distance and direction are used, there occur some changes in precision depending on changes in relative distance when determining the relative position. As a result of simulation, it was possible to determine the relative position with several millimeter-level errors at a distance of 10 km, and sub-millimeter level errors at a distance of 1 km. In addition, we performed the determination of relative position assuming the case that global positioning system data was not received for long hours to see the impact of determination of chief satellite orbit on the determination of relative position. The determination of precise relative position at a long distance carried out in this study can be used for scientific mission using the satellite formation flying

Compliance and persistence with oral bisphosphonates for the treatment of osteoporosis in female patients with rheumatoid arthritis

Abstract Background Poor adherence with oral bisphosphonates (BPs) can mitigate their therapeutic benefit for osteoporosis and is a significant clinical burden. Most previous studies regarding adherence with oral BPs have focused on postmenopausal osteoporosis, but little attention has been given to patients with rheumatoid arthritis (RA). Thus, we investigated compliance and persistence with oral BPs in the treatment of osteoporosis and analyzed risk factors for poor adherence in female patients with (RA) in real setting. Methods This is a retrospective longitudinal study including 396 female patients with RA in whom oral BPs were newly initiated from Aug 2004 to Aug 2014 at a university rheumatology center in South Korea. Compliance was quantified using the 1-year medication possession ratio (MPR), while persistence was defined as duration from the initiation to the end of BPs therapy without interruption exceeding 56 days. Seropositve RA was defined as having a positive test result for the presence of either rheumatoid factor or anti-cyclic citrullinated peptide antibody. Results Of 396 RA patients, 221 (55.8%) were prescribed risedronate 35 mg weekly; 17 (4.3%) received alendronate 70 mg weekly; and 158 (39.9%) received ibandronate 150 mg monthly. The 1-year MPR was 70.1% and the proportion of RA patients with the 1-year MPR ≥ 0.8 was 60.1%. A total of 274 (69.2%) patients discontinued oral BPs during the study period and persistence with BPs was 63.3% at 1 year, 50.7% at 2 years and 33.3% at 3 years. The most common cause of non-persistence was adverse events (47.5%), followed by poor health literacy (40.5%) and cost (12%). Both compliance and persistence with monthly oral BPs were significantly lower than those with weekly regimens (OR: 2.48, 95% CI: 1.59–3.89, P < 0.001 and HR: 2.19, 95% CI: 1.69–2.83, P < 0.001, respectively). Additionally, patients with seropositive RA showed better compliance and persistence with BPs compared with their seronegative counterparts. Conclusions Compliance and persistence with oral BPs in RA patients were suboptimal in real practice, thereby limiting the efficacy of osteoporosis treatment. Extending the dosing interval of BPs may improve medication adherence in RA patients

Uncooled Short-Wave Infrared Sensor Based on PbS Quantum Dots Using ZnO NPs

Shortwave infrared (SWIR) sensors have attracted interest due to their usefulness in applications like military and medical equipment. SWIR sensors based on various materials are currently being studied. However, most SWIR detectors need additional optical filters and cooling systems to detect specific wavelengths. In order to overcome these limitations, we proposed a solution processed SWIR sensor that can operate at room temperature using lead chloride (PbS) QDs as a photoactive layer. Additionally, we adapted zinc oxide (ZnO) nanoparticles (NPs) as an electron transport layer (ETL) to improve the sensitivity of a PbS SWIR sensor. In this study, PbS SWIR sensors with and without a ZnO NPs layer were fabricated and their current&ndash;voltage (I&ndash;V) characteristics were measured. The on/off ratio of the PbS SWIR sensor with ZnO NPs was 2.87 times higher than that of the PbS SWIR sensor without ZnO NPs at the maximum current difference. The PbS SWIR sensor with ZnO NPs showed more stable current characteristics than that without ZnO NPs because of the ZnO NPs&rsquo; high electron mobility and proper lowest unoccupied molecular orbital (LUMO) level