P1, N170, and N250 Event-related Potential Components Reflect Temporal Perception Processing in Face and Body Personal Identification.

Human faces and bodies represent various socially important signals. Although adults encounter numerous new people in daily life, they can recognize hundreds to thousands of different individuals. However, the neural mechanisms that differentiate one person from another person are unclear. This study aimed to clarify the temporal dynamics of the cognitive processes of face and body personal identification using face-sensitive ERP components (P1, N170, and N250). The present study performed three blocks (face-face, face-body, and body-body) of different ERP adaptation paradigms. Furthermore, in the above three blocks, ERP components were used to compare brain biomarkers under three conditions (same person, different person of the same sex, and different person of the opposite sex). The results showed that the P1 amplitude for the face-face block was significantly greater than that for the body-body block, that the N170 amplitude for a different person of the same sex condition was greater than that for the same person condition in the right hemisphere only, and that the N250 amplitude gradually increased as the degree of face and body sex-social categorization grew closer (i.e., same person condition > different person of the same sex condition > different person of the opposite sex condition). These results suggest that early processing of the face and body processes the face and body separately and that structural encoding and personal identification of the face and body process the face and body collaboratively.

Asymptomatic cable twisting in a patient with impending Twiddler syndrome detected during deep brain stimulation surgery for Parkinson's disease: A case report.

Background: Deep brain stimulation (DBS) has consistently demonstrated high efficacy and safety in patients with Parkinson's disease. Twiddler's syndrome is a rare occurrence of hardware failure in patients undergoing neuromodulation. We report here a case of subclinical cable twisting jeopardizing Twiddler's syndrome in a patient with Parkinson's disease who underwent DBS surgery targeting the globus pallidus internus (GPI). Case Description: A 70-year-old woman with a 7-year history of Parkinson's disease refractory to medication was referred to our department for treatment of involuntary movements of the left hand and leg. She underwent right GPI DBS implantation. Left GPI DBS implantation was subsequently planned to manage resting tremors that developed in the right leg after the first surgery at around one year after the first surgery. During a routine check-up before the second surgery, we incidentally detected Twiddler's syndrome. The patient showed no neurological deficits in the left extremities, the same as before right GPI DBS. We performed left GPI DBS concomitantly with the revision of the implantable pulse generator and extension wire. Conclusion: Twiddler's syndrome is a rare complication of DBS. Subclinical risk of cable twisting jeopardizing Twiddler's syndrome is rarely detected without clinical indications of hardware failure. Neurosurgeons should be cognizant of and regularly monitor the implanted device in case serious complications occur.

Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: the influence of alcohol consumption.

BACKGROUND/AIMS: Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. We previously reported that pemafibrate significantly improves liver function, serum triglyceride (TG) levels and liver stiffness in non-alcoholic fatty liver disease patients, however the influence of alcohol consumption was not considered. Therefore, we explored pemafibrate efficacy in patients with steatotic liver disease (SLD) and alcohol-associated liver disease (ALD). METHODS: We retrospectively evaluated pemafibrate efficacy on liver enzymes and lipids in metabolic dysfunction-associated SLD (MASLD) (n = 93), MASLD plus increased alcohol intake (MetALD; n = 23) and ALD (n = 22) patients who had taken pemafibrate for at least 48 weeks. Liver shear wave velocity (SWV, n = 75) was also evaluated. RESULTS: In MASLD group, ALT, aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and TG values were significantly decreased from baseline to week 24 and week 48 ( P  < 0.0001). ALT and TG values in MetALD group and ALT and AST values in ALD group were also significantly decreased from baseline to week 24 and week 48. Study participant SWV values decreased from baseline to week 48. We observed no significant difference in changes to ALT, AST, γ-GTP and TG (value at week 24 or week 48 minus value at baseline) among the three groups. CONCLUSION: Pemafibrate improves liver function and liver stiffness thus making it a promising therapeutic agent for SLD, even in patients with excess alcohol consumption (MetALD and ALD groups).

Pre-operative Serum Albumin Predicts Native Liver Survival in Biliary Atresia.

BACKGROUND: To predict native liver survival (NLS) after Kasai portoenterostomy (KP) for biliary atresia (BA) using pre-operative clinical data. METHODS: Pre-operative data were collected from 29 patients with BA who underwent KP at our department between 1989 and 2017 and were analysed including serum albumin, bilirubin, prothrombin time-international normalised ratio, body height, body weight, age at KP, paediatric end-stage liver disease score calculated using the pre-operative data and the period of NLS. RESULTS: The 10-year NLS rate of all patients was 51%. A multivariate analysis revealed that among all factors, the pre-KP serum albumin level was the only independent predictor of NLS (P = 0.04, hazard ratio = 0.269, 95% confidence interval = 0.077-0.934). The area under the receiver operating characteristic curve for NLS, determined using pre-KP serum albumin was 0.760 and 3.75 mg/dl was selected as the cut-off value. There was a significant difference in NLS between patients with high (≥3.8 mg/dl) and low (≤3.7 mg/dl) pre-KP serum albumin (90.0% vs. 31.5%, P < 0.01). CONCLUSIONS: Decreased pre-KP serum albumin may reflect not only functional impairment of the liver, but also the inflammatory process, which is hypothesized to occur during its advancement. The pre-KP serum albumin level may be a good prognostic factor for NLS in post-KP BA patients.

Brca2(p.T1942fs/+) dissipates ovarian reserve in rats through oxidative stress in follicular granulosa cells.

Pathogenic variants of BRCA1/2 constitute hereditary breast and ovarian cancer (HBOC) syndrome, and BRCA1/2 mutant is a risk for various cancers. Whereas the clinical guideline for HBOC patients has been organized for the therapy and prevention of cancer, there is no recommendation on the female reproductive discipline. Indeed, the role of BRCA1/2 pathogenic variants in ovarian reserve has not been established due to the deficiency of appropriate animal models. Here, we used a rat model of Brca2(p.T1942fs/+) mutant of Sprague-Dawley strain with CRISPR-Cas9 editing to evaluate ovarian reserve in females. Fertility and ovarian follicles were evaluated and anti-Müllerian hormone (AMH) was measured at 8-32 weeks of age with a comparison between the wild-type and the mutant rats (MUT). MUT revealed a significantly smaller number of deliveries with fewer total pups. Furthermore, MUT showed a significant decrease in primordial follicles at 20 weeks and a low AMH level at 28 weeks. RNA-sequencing of the ovary at 10 weeks detected acceleration of the DNA damage repair pathway, which was accompanied by oxidative stress-induced DNA double-strand breaks, a decrease in PTEN, and an increase in mTOR in follicular granulosa cells. In conclusion, Brca2(p.T1942fs/+) dissipates primordial follicles via early activation of granulosa cells through oxidative stress, leading to earlier termination of fertility.

Microlesion Effect Induced by Electrode Implantation in the Posteroventral Globus Pallidus Interna for Severe Dystonic Tics.

Background: Tourette syndrome (TS) is a neurologic condition characterized by motor and phonic tics. Dystonic tics, including blepharospasm, are considered atypical or unusual in severe TS. Case Report: We report a severe case of TS with facial dystonic tics resembling blepharospasm in which the microlesion effect and a sustained therapeutic effect was observed with bilateral globus pallidus interna (GPi) deep brain stimulation (DBS). Discussion: Bilateral GPi DBS can be beneficial for blepharospasm-like tics and severe symptoms of TS. The improvements seen can be explained by the microlesion effect induced by DBS lead placement in the GPi.

Serum Zinc-α2-glycoprotein Levels Are Associated with the Hepatorenal Function and Predict the Survival in Cases of Chronic Liver Disease.

Objective Zinc-α2-glycoprotein (ZAG) is secreted by various organs, such as liver, kidney and adipose tissue, is involved in lipolysis, and may contribute to the pathogenesis of chronic liver disease (CLD). We therefore assessed whether or not ZAG is a surrogate marker for the hepatorenal function, body composition and all causes of mortality, as well as complications, including ascites, hepatic encephalopathy (HE) and portosystemic shunts (PSS) in CLD. Methods Serum ZAG levels were measured in 180 CLD patients upon hospital admission. The associations of ZAG levels with the liver functional reserve and clinical parameters were investigated using a multiple regression analysis. Kaplan-Meier analyses were performed to evaluate the associations of the ZAG/creatinine ratio (ZAG/Cr) and prognostic factors with mortality. Results High serum ZAG levels were associated with preserving the liver function and renal insufficiency. A multiple regression analysis showed that the estimated glomerular filtration rate (p<0.0001), albumin-bilirubin (ALBI) score (p=0.0018) and subcutaneous fat area (p=0.0023) had a significant independent correlation with serum ZAG levels. Serum ZAG levels were elevated in the absence of HE (p=0.0023) and PSS (p=0.0003). In all patients and those without hepatocellular carcinoma (HCC), the cumulative mortality rate was significantly decreased in patients with a high ZAG/Cr compared with those with a low ZAG/Cr (p=0.0018 and p=0.0002, respectively). The ZAG/Cr, presence of HCC, ALBI score and psoas muscle index were independent predictors of the prognosis in CLD patients. Conclusion Serum ZAG levels are associated with the hepatorenal function and can be used to predict the survival in CLD patients.

Assessment of Residual Vasospasm in Patients with Plaque Rupture or Plaque Erosion using Optical Coherence Tomography.

AIMS: Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT). METHODS: We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified. RESULTS: The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm2; P=0.05) than wavy patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI. CONCLUSION: Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.

INTRACOLON COOLING INCREASES SURVIVAL RATE IN THE RAT MODEL OF LETHAL HEMORRHAGE.

ABSTRACT: Background: The objective of this study was to investigate whether transrectal intracolon (TRIC) cooling can prolong the survival duration in a rat hemorrhagic shock (HS) model. Methods: A lethal HS was induced by bleeding 47% of the total blood volume. A TRIC device was placed into the colon to maintain the intracolon temperature either at 37°C (TRIC37) or at 10°C (TRIC10) post-HS. In the surface cooling (SC) rats, the body temperatures were maintained at the same level as the esophageal temperature of the TRIC10 rats. A separated group of TRIC10 rats were resuscitated (Res) at 90 min post-HS. A total of six groups were as follows: (i) Sham TRIC37 (n = 5), (ii) Sham TRIC10 (n = 5), (iii) HS TRIC37 (n = 5), (iv) HS TRIC10 (n = 6), (v) HS SC (n = 6), and (vi) HS TRIC10 + Res (n = 6). Results: An average post-HS survival time was 18.4 ± 9.4 min in HS TRIC37 and 82 ± 27.82 min in the HS SC group. In striking contrast, the HS TRIC10 group exhibited an average survival time of 150.2 ± 66.43 min. The post-HS blood potassium level rose significantly in the HS TRIC37 and HS SC, whereas it remained unchanged in the TRIC10 groups. Post-HS intestinal damage occurred in HS TRIC37 and HS SC groups but virtually absent in HS TRIC10 groups. After resuscitation at 90 min post-HS, all HS TRIC10 rats were fully recovered from the lethal HS. Conclusions: TRIC10 reversed the high blood potassium level, prevented the intestinal damage, and prolonged the survival duration by sixfold relative to normothermia and by twofold compared with SC post-HS. All TRIC10 rats were successfully resuscitated at 90 min post-HS.

Wireless point-of-care ultrasound in a multiplace hyperbaric chamber.

Background: Electronic devices remain highly restricted from use during hyperbaric oxygen (HBO2) treatment due to risk of fire in a pressurized, oxygen-rich environment. Over recent decades, point-of- care ultrasound (POCUS) has established utility in most clinical environments except hyperbaric chambers, where only heavily modified POCUS devices have been used. This study evaluated proof of concept, safety, and performance of a wireless off-the-shelf handheld POCUS device in the hyperbaric environment. Materials and Methods: The GE Vscan Air was initially tested in a Class C chamber with 100% nitrogen up to 4.0 ATA and monitored. Second, the Vscan Air was paired with an encased Apple iPad, tested previously for hyperbaric use, and both were pressurized to 2.4 ATA in a Class A chamber (21% oxygen) and evaluated. Similarly, it was then tested at 2.8 ATA and also paired wirelessly with an iPad outside the chamber. Device temperature, image quality, functionality, and wireless connection were tested continuously. Results: The GE Vscan Air automatically shut off due to power button depression during initial compression; thus the power button was punctured with an 18-gauge needle to equalize gas pressure. Thereafter, the system performed well throughout all tests without degradation in function or image quality. The device did not overheat nor reach temperatures concerning for fire hazard. Further, wireless connection to out-of-chamber devices was maintained. Conclusions: Our results suggest that the GE Vscan Air can be used with minor modification in a multi- place hyperbaric chamber. Wireless functionality allows for pairing with a screen and device outside the chamber.

Programmable Self-Assembly of Nanoplates into Bicontinuous Nanostructures.

Self-assembly is the process by which individual components arrange themselves into an ordered structure by changing the shapes, components, and interactions. It has enabled us to construct an extensive range of geometric forms on many length scales. Nevertheless, the potential of two-dimensional polygonal nanoplates to self-assemble into extended three-dimensional structures with compartments and corridors has remained unexplored. In this paper, we show coarse-grained Monte Carlo simulations demonstrating self-assembly of hexagonal/triangular nanoplates via complementary interactions into faceted, sponge-like "bicontinuous polyhedra" (or infinite polyhedra) whose flat walls partition space into a pair of mutually interpenetrating labyrinths. Two bicontinuous polyhedra can be self-assembled: the regular (or Platonic) Petrie-Coxeter infinite polyhedron (denoted {6,4|4}) and the semi-regular Hart "gyrangle". The latter structure is chiral, with both left- and right-handed versions. We show that the Petrie-Coxeter assembly is constructed from two complementary populations of hexagonal nanoplates. Furthermore, we find that the 3D chiral Hart gyrangle can be assembled from identical achiral triangular nanoplates decorated with regioselective complementary interaction sites. The assembled Petrie-Coxeter and Hart polyhedra are faceted versions of two of the simplest triply periodic minimal surfaces, namely, Schwarz's primitive and Schoen's gyroid surfaces, respectively, offering alternative routes to those bicontinuous nanostructures, which are widespread in synthetic and biological materials.

Advances in pediatric liver transplantation from the pediatric surgeon's perspective.

Pediatric liver transplantation is a lifesaving state-of-the-art operation for children with various liver diseases, including cholestatic diseases, metabolic disorders, acute liver failure, and primary malignant liver tumors. Among these indications, transplantation for biliary atresia and hepatoblastoma is discussed in this review because pediatric surgeons are usually involved in their initial treatments. For biliary atresia, pediatric surgeons are advised to keep dissection of the hilar structures to a minimum during Kasai portoenterostomy in order to make total hepatectomy easier at transplantation. Early referral to a transplant team is recommended when worrisome signs of liver dysfunction, cirrhosis, portal hypertension and growth retardation are noted. Hepatoblastoma with multiplicity or located close to major vessels may indicate unresectability, and the transplant team needs to be consulted early after neoadjuvant chemotherapy is started. The graft size, including its thickness, needs to be evaluated before transplantation for small children, as tailoring the shape of the partial graft may be necessary during the transplant procedure.

Crystal structure of the stalk region of axonemal inner-arm dynein-d reveals unique features in the coiled-coil and microtubule-binding domain.

Axonemal dynein is an ATP-dependent microtubular motor protein responsible for cilia and flagella beating, and its dysfunction can cause diseases such as primary ciliary dyskinesia and sperm dysmotility. Despite its biological importance, structure-based mechanisms underlying axonemal dynein motors remain unclear. Here, we determined the X-ray crystal structure of the human inner-arm dynein-d (DNAH1) stalk region, which contains a long antiparallel coiled-coil and a microtubule-binding domain (MTBD), at 2.7 Å resolution. Notably, differences in the relative orientation of the coiled-coil and MTBD in comparison with other dyneins, as well as the diverse orientations of the MTBD flap region among various isoforms, lead us to propose a 'spike shoe model' with an altered stepping angle for the interaction between IAD-d and microtubules. Based on these findings, we discuss isoform-specific functions of the axonemal dynein stalk MTBDs.

Three structures of PSI-LHCI from Chlamydomonas reinhardtii suggest a resting state re-activated by ferredoxin.

Photosystem I (PSI) from the green alga Chlamydomonas reinhardtii, with various numbers of membrane bound antenna complexes (LHCI), has been described in great detail. In contrast, structural characterization of soluble binding partners is less advanced. Here, we used X-ray crystallography and single particle cryo-EM to investigate three structures of the PSI-LHCI supercomplex from Chlamydomonas reinhardtii. An X-ray structure demonstrates the absence of six chlorophylls from the luminal side of the LHCI belts, suggesting these pigments were either physically absent or less stably associated with the complex, potentially influencing excitation transfer significantly. CryoEM revealed extra densities on luminal and stromal sides of the supercomplex, situated in the vicinity of the electron transfer sites. These densities disappeared after the binding of oxidized ferredoxin to PSI-LHCI. Based on these structures, we propose the existence of a PSI-LHCI resting state with a reduced active chlorophyll content, electron donors docked in waiting positions and regulatory binding partners positioned at the electron acceptor site. The resting state PSI-LHCI supercomplex would be recruited to its active form by the availability of oxidized ferredoxin.

Integrated proteomics identifies p62-dependent selective autophagy of the supramolecular vault complex.

In addition to membranous organelles, autophagy selectively degrades biomolecular condensates, in particular p62/SQSTM1 bodies, to prevent diseases including cancer. Evidence is growing regarding the mechanisms by which autophagy degrades p62 bodies, but little is known about their constituents. Here, we established a fluorescence-activated-particle-sorting-based purification method for p62 bodies using human cell lines and determined their constituents by mass spectrometry. Combined with mass spectrometry of selective-autophagy-defective mouse tissues, we identified vault, a large supramolecular complex, as a cargo within p62 bodies. Mechanistically, major vault protein directly interacts with NBR1, a p62-interacting protein, to recruit vault into p62 bodies for efficient degradation. This process, named vault-phagy, regulates homeostatic vault levels in vivo, and its impairment may be associated with non-alcoholic-steatohepatitis-derived hepatocellular carcinoma. Our study provides an approach to identifying phase-separation-mediated selective autophagy cargoes, expanding our understanding of the role of phase separation in proteostasis.

Soluble domains of cytochrome c-556 and Rieske iron-sulfur protein from Chlorobaculum tepidum: Crystal structures and interaction analysis.

In photosynthetic green sulfur bacteria, the electron transfer reaction from menaquinol:cytochrome c oxidoreductase to the P840 reaction center (RC) complex occurs directly without any involvement of soluble electron carrier protein(s). X-ray crystallography has determined the three-dimensional structures of the soluble domains of the CT0073 gene product and Rieske iron-sulfur protein (ISP). The former is a mono-heme cytochrome c with an α-absorption peak at 556 nm. The overall fold of the soluble domain of cytochrome c-556 (designated as cyt c-556sol) consists of four α-helices and is very similar to that of water-soluble cyt c-554 that independently functions as an electron donor to the P840 RC complex. However, the latter's remarkably long and flexible loop between the α3 and α4 helices seems to make it impossible to be a substitute for the former. The structure of the soluble domain of the Rieske ISP (Rieskesol protein) shows a typical ß-sheets-dominated fold with a small cluster-binding and a large subdomain. The architecture of the Rieskesol protein is bilobal and belongs to those of b6f-type Rieske ISPs. Nuclear magnetic resonance (NMR) measurements revealed weak non-polar but specific interaction sites on Rieskesol protein when mixed with cyt c-556sol. Therefore, menaquinol:cytochrome c oxidoreductase in green sulfur bacteria features a Rieske/cytb complex tightly associated with membrane-anchored cyt c-556.

Polymorphism of genes encoding drug-metabolizing and inflammation-related enzymes for susceptibility to cholangiocarcinoma in Thailand.

BACKGROUND: Cholangiocarcinoma (CCA) is an intractable cancer, and its incidence in northeastern Thailand is the highest worldwide. Infection with the liver fluke Opisthorchis viverrini (OV) has been associated with CCA risk. However, animal experiments have suggested that OV alone does not induce CCA, but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters. Therefore, in humans, other environmental and genetic factors may also be involved. AIM: To examine relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes. METHODS: This hospital-based case-control study enrolled 95 case-control pairs matched by age (± 5 years) and sex. We examined relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes, serum anti-OV, alcohol consumption, and smoking. Polymorphisms of CYP2E1, IL-6 (-174 and -634), IL-10 (-819), and NF-κB (-94) and their co-occurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed. RESULTS: Although CCA risk was not significantly associated with any single polymorphism, persons with the GSTT1 wild-type and CYP2E1 c1/c2 + c2/c2 genotype had an increased risk (OR = 3.33, 95%CI: 1.23-9.00) as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype. The presence of anti-OV in serum was associated with a 7- to 11-fold increased risk, and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms. CONCLUSION: In addition to infection with OV, gene-gene interactions may be considered as one of the risk factors for CCA development.