Clinical importance of F-waves as a prognostic factor in Guillain-Barré syndrome in children

PurposeA limited number of studies have examined the link between F-wave abnormalities and clinical presentation in pediatric Guillain-Barré syndrome (GBS). Therefore, this study examined the importance of F-wave abnormalities as a prognostic factor in pediatric GBS patients.MethodsThe records and electrodiagnostic studies (EDS) of 70 GBS patients were retrospectively evaluated, and divided into 2 groups according to the results of EDS. Group A (n=33) presented with F-wave abnormalities, and group B (n=26) exhibited normal findings. We compared laboratory reports, clinical features, response to treatment, and prognosis between the 2 groups.ResultsMotor weakness was the most frequently observed symptom for either group. Clinically, the incidence of fever and upper respiratory symptoms differed between the 2 groups, while the prevalence of abnormal deep tendon reflex (DTR) was significantly higher in group A than B (P<0.05). Patients diagnosed with GBS had received intravenous immunoglobulin treatment: 94% in group A and 58% in group B. Furthermore, significantly greater numbers of patients in group A showed H-reflex abnormalities and poor prognosis compared with group B (P<0.05).ConclusionThis study demonstrated that F-waves are a clinically important prognostic factor in GBS. F-wave abnormalities were associated with abnormal DTR and poor prognosis in patients. Limited studies have examined the link between F-wave abnormalities and clinical results; therefore, further randomized controlled studies are needed to confirm the clinical characteristics and efficacy of treatments

Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1–Syk and p62/SQSTM1

Numerous atypical mycobacteria, including Mycobacterium abscessus (Mabc), cause nontuberculous mycobacterial infections, which present a serious public health threat. Inflammasome activation is involved in host defense and the pathogenesis of autoimmune diseases. However, inflammasome activation has not been widely characterized in human macrophages infected with atypical mycobacteria. Here, we demonstrate that Mabc robustly activates the nucleotide binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold protein p62/SQSTM1 (p62) in human macrophages. Both dectin-1 and Toll-like receptor 2 (TLR2) were required for Mabc-induced mRNA expression of pro-interleukin (IL)-1β, cathelicidin human cationic antimicrobial protein-18/LL-37 and β-defensin 4 (DEFB4). Dectin-1-dependent Syk signaling, but not that of MyD88, led to the activation of caspase-1 and secretion of IL-1β through the activation of an NLRP3/apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) inflammasome. Additionally, potassium efflux was required for Mabc-induced NLRP3/ASC inflammasome activation. Furthermore, Mabc-induced p62 expression was critically involved in NLRP3 inflammasome activation in human macrophages. Finally, NLRP3/ASC was critical for the inflammasome in antimicrobial responses to Mabc infection. Taken together, these data demonstrate the induction mechanism of the NLRP3/ASC inflammasome and its role in innate immunity to Mabc infection

Absence of pain in subjects with advanced radiographic knee osteoarthritis

Background To investigate the frequency of pain among subjects with advanced radiographic knee osteoarthritis (OA) defined as Kellgren–Lawrence (KL) grade 4 and clinical features associated with pain. Methods Subjects from the Hallym Aging Study (HAS), the Korean National Health and Nutrition Examination Survey (KNHANES), and the Osteoarthritis Initiative (OAI) were included. Participants were asked knee-specific questions regarding the presence of knee pain. Clinical characteristics associated with the presence of pain were evaluated with multivariable logistic regression analysis. Results The study population consisted of 504, 10,152 and 4796 subjects from HAS, KNHANES, and OAI, respectively. KL grade 4 OA was identified in 9.3, 7.6, and 11.5% of subjects, while pain was absent in 23.5, 31.2, and 5.9% of subjects in KL grade 4 knee OA, respectively. After multivariable analysis, female gender showed a significant association with pain in the KNHANES group, while in the OAI group, younger age did. Advanced knee OA patients without pain did not differ from non-OA subjects in most items of SF-12 in both Korean and OAI subjects. Total WOMAC score was not significantly different between non-OA and advanced knee OA subjects without pain in the OAI. Conclusions Our study showed that a considerable number of subjects with KL grade 4 OA did not report pain. In patients whose pain arises from causes other than structural damage of the joint, therapeutic decision based on knee X-ray would lead to suboptimal result. In addition, treatment options focusing solely on cartilage engineering, should be viewed with caution.This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI16C0287), a grant of the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1A2B2001881), and Hallym University research fun

Performance evaluation of SimPET-L and SimPET-XL: MRI-compatible small-animal PET systems with rat-body imaging capability

Background SimPET-L and SimPET-XL have recently been introduced with increased transaxial fields of view (FOV) compared with their predecessors (SimPET™ and SimPET-X), enabling whole-body positron emission tomography (PET) imaging of rats. We conducted performance evaluations of SimPET-L and SimPET-XL and rat-body imaging with SimPET-XL to demonstrate the benefits of increased axial and transaxial FOVs. Procedures The detector blocks in SimPET-L and SimPET-XL consist of two 4 × 4 silicon photomultiplier arrays coupled with 20 × 9 array lutetium oxyorthosilicate crystals. SimPET-L and SimPET-XL have an inner diameter (bore size) of 7.6cm, and they are composed of 40 and 80 detector blocks yielding axial lengths of 5.5 and 11cm, respectively. Each system was evaluated according to the National Electrical Manufacturers Association NU4-2008 protocol. Rat imaging studies, such as 18F-NaF and 18F-FDG PET, were performed using SimPET-XL. Results The radial resolutions at the axial center measured using the filtered back projection, 3D ordered-subset expectation maximization (OSEM), and 3D OSEM with point spread functions correction were 1.7, 0.82, and 0.82mm FWHM in SimPET-L and 1.7, 0.91, and 0.91mm FWHM in SimPET-XL, respectively. The peak sensitivities of SimPET-L and SimPET-XL were 6.30% and 10.4% for an energy window of 100–900keV and 4.44% and 7.25% for a window of 250–750keV, respectively. The peak noise equivalent count rate with an energy window of 250–750keV was 249kcps at 44.9MBq for SimPET-L and 349kcps at 31.3MBq for SimPET-XL. In SimPET-L, the uniformity was 4.43%, and the spill-over ratios in air- and water-filled chambers were 5.54% and 4.10%, respectively. In SimPET-XL, the uniformity was 3.89%, and the spill-over ratio in the air- and water-filled chambers were 3.56% and 3.60%. Moreover, SimPET-XL provided high-quality images of rats. Conclusion SimPET-L and SimPET-XL show adequate performance compared with other SimPET systems. In addition, their large transaxial and long axial FOVs provide imaging capability for rats with high image quality.This work was supported by a Korea Medical Device Development Fund grant funded by the Korean government (Ministry of Science and ICT; Ministry of Trade, Industry and Energy; Ministry of Health & Welfare; Ministry of Food and Drug Safety) (Project Numbers: 1711137868 and RS-2020-KD000006), and the Korea Brain Research Institute Basic Research Program through KBRI funded by the Ministry of Science and ICT (Grant No. 22-BR-05-02)

Cereblon deficiency ameliorates carbon tetrachloride-induced acute hepatotoxicity in HepG2 cells by suppressing MAPK-mediated apoptosis

The liver is vulnerable to various hepatotoxins, including carbon tetrachloride (CCl4), which induces oxidative stress and apoptosis by producing reactive oxygen species (ROS) and activating the mitogen-activated protein kinase (MAPK) pathway. Cereblon (CRBN), a multifunctional protein implicated in various cellular processes, functions in the pathogenesis of various diseases; however, its function in liver injury remains unknown. We established a CRBN-knockout (KO) HepG2 cell line and examined its effect on CCl4-induced hepatocellular damage. CRBN-KO cells exhibited reduced sensitivity to CCl4-induced cytotoxicity, as evidenced by decreased levels of apoptosis markers, such as cleaved caspase-3, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. CRBN deficiency enhanced antioxidant defense, with increased superoxide dismutase activity and glutathione ratios (GSH/GSSG), as well as reduced pro-inflammatory cytokine expression. Mechanistically, the protective effects of CRBN deficiency appeared to involve the attenuation of the MAPK-mediated pathways, particularly through decreased phosphorylation of JNK and ERK. Overall, these results suggest the crucial role of CRBN in mediating the hepatocellular response to oxidative stress and inflammation triggered by CCl4 exposure, offering potential clinical implications for liver injury in a wide range of liver diseases

Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein (RNP) electroporation

Background Genome editing has been considered as powerful tool in agricultural fields. However, genome editing progress in cattle has not been fast as in other mammal species, for some disadvantages including long gestational periods, single pregnancy, and high raising cost. Furthermore, technically demanding methods such as microinjection and somatic cell nuclear transfer (SCNT) are needed for gene editing in cattle. In this point of view, electroporation in embryos has been risen as an alternative. Results First, editing efficiency of our electroporation methods were tested for embryos. Presence of mutation on embryo was confirmed by T7E1 assay. With first combination, mutation rates for MSTN and PRNP were 57.6% ± 13.7% and 54.6% ± 13.5%, respectively. In case of MSTN/BLG, mutation rates were 83.9% ± 23.6% for MSTN, 84.5% ± 18.0% for BLG. Afterwards, the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing. Thirteen recipients were transferred for MSTN/PRNP, 4 calves were delivered, and one calf underwent an induction for double KO. Ten surrogates were given double-KO embryos for MSTN/BLG, and four of the six calves that were born had mutations in both genes. Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied. Finally, MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.This study was financially supported by the National Research Foundation of Korea (NRF-2021R1A5A1033157 for SRC program: 382 Comparative medicine Disease Research Center; NRF-2021R1F1A105195313), the Research Institute of Veterinary Science, the BK21 Four for Future Veterinary Medicine Leading Education and Research Center, and a Seoul National University (SNU) grant (#550e2020005