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The role of torso computed tomography (CT) in evaluating body composition has been unexplored. This study assessed the potential of low-dose torso CT from positron emission tomography (PET)/CT for analyzing body composition and its relation to muscle strength. We retrospectively recruited 384 healthy Korean adults (231 men, 153 women) who underwent torso 18F-FDG PET/CT, bioelectrical impedance analysis (BIA), and muscle strength tests (handgrip strength [HGS] and knee extension strength [KES]). CT images were segmented into three compartments: torso volumetric, abdominal volumetric, and abdominal areal. Muscle amounts from each compartment were indexed to height (m2). BIA and HGS served as reference standards, with correlation coefficients (r) calculated. Torso muscle volumetric index (TorsoMVI) had the strongest correlations with BIA-derived values (r = 0.80 for men; r = 0.73 for women), surpassing those from the abdominal compartments. TorsoMVI was also correlated significantly with HGS (r = 0.39, p < 0.01) and differentiated between normal and possible sarcopenia in men (n = 225, 5960 ± 785 cm3/m2 vs. n = 6, 5210 ± 487 cm3/m2, p = 0.02). In women, KES correlated more strongly with muscle parameters than HGS. Despite gender-specific variations, torso CT-derived parameters show promise for evaluating body composition and sarcopenia. [ABSTRACT FROM AUTHOR]

18F-FP-CIT is a high-resolution imaging marker of nigrostriatal neuronal integrity, differentiating Parkinsonism with loss of dopaminergic terminals (presynaptic Parkinsonian syndrome [PS]) from Parkinsonism without nigrostriatal degeneration (non-PS). We assessed the diagnostic accuracy of 18F-FP-CIT PET in patients with clinically uncertain PS (CUPS) at the first visit. Among the 272 patients who underwent 18F-FP-CIT PET imaging at the first visit between September 2008 and July 2012, 111 had CUPS (age, 62.6 ± 10.5 y; male:female, 45:66; symptom duration, 13.1 ± 8.8 months). Uncertainty criteria included only one of the three cardinal signs of Parkinsonism, two signs without bradykinesia, or atypical signs. The baseline clinical and 18F-FP-CIT PET imaging diagnostic accuracy was compared with the accuracy of clinical diagnosis after > 2-year follow-up. Nuclear medicine physicians assessed the 18F-FP-CIT PET images visually. Focal dopamine transporter binding deficit in the posterior putamen was considered PS. Bilateral symmetric striatum without focal deficit, suggesting normal 18F-FP-CIT PET, and focal deficits elsewhere in the striatum suggesting vascular Parkinsonism were considered non-PS. Seventy-nine patients had PS, and 32 did not. Baseline clinical diagnosis included PS in 45 patients, non-PS in 24, and inconclusive in 42. Among patients in whom initial clinical diagnosis (PS or non-PS) was possible, the sensitivity, specificity, and accuracy of the baseline clinical and 18F-FP-CIT PET imaging diagnoses were 54.4, 50.0, and 53.2%, and 98.7, 100, and 99.1%, respectively. The respective positive and negative predictive values were 95.6 and 66.7%, and 100 and 97.0%. Among those with initially inconclusive diagnosis, 64.2% were eventually diagnosed with PS while 35.7% were diagnosed with non-PS. The final clinical diagnosis of these patients all matched those made by 18F-FP-CIT PET imaging, except in one patient with scan without evidence of dopaminergic deficit (SWEDD). 18F-FP-CIT PET diagnosis was more accurate than clinical diagnosis, reducing the false-negative and inconclusive clinical diagnosis rates at baseline in patients with CUPS. [ABSTRACT FROM AUTHOR]

We developed a novel quantification method named "shape feature" by combining the features of amyloid positron emission tomography (PET) and brain magnetic resonance imaging (MRI) and evaluated its significance in predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. From the ADNI database, 334 patients with MCI were included. The brain amyloid smoothing score (AV45_BASS) and brain atrophy index (MR_BAI) were calculated using the surface area and volume of the region of interest in AV45 PET and MRI. During the 48-month follow-up period, 108 (32.3%) patients converted from MCI to AD. Age, Mini-Mental State Examination (MMSE), cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), apolipoprotein E (APOE), standardized uptake value ratio (SUVR), AV45_BASS, MR_BAI, and shape feature were significantly different between converters and non-converters. Univariate analysis showed that age, MMSE, ADAS-cog, APOE, SUVR, AV45_BASS, MR_BAI, and shape feature were correlated with the conversion to AD. In multivariate analyses, high shape feature, SUVR, and ADAS-cog values were associated with an increased risk of conversion to AD. In patients with MCI in the ADNI cohort, our quantification method was the strongest prognostic factor for predicting their conversion to AD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated. A cell viability assay showed that LCD had anti-apoptotic properties in MG132-induced oxidative-stressed pNSCs. It was confirmed that apoptosis was reduced in pNSCs treated with LCD through 7-AAD/Annexin Ⅴ staining and cleaved caspase3. These effects of LCD were mediated through an interaction with JunD and through the EGFR/AKT and JNK signaling pathways. These findings suggest that LCD could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD. [ABSTRACT FROM AUTHOR]

The concept of cognitive reserve (CR) has been proposed as a protective factor that modifies the effect of brain pathology on cognitive performance. It has been characterized through CR proxies; however, they have intrinsic limitations. In this study, we utilized two different datasets containing tau, amyloid PET, and T1 magnetic resonance imaging. First, 91 Alzheimer's disease (AD) continuum subjects were included from Alzheimer's Disease Neuroimaging Initiative 3. CR was conceptualized as the residual between actual cognition and estimated cognition based on amyloid, tau, and neurodegeneration. The proposed marker was tested by the correlation with CR proxy and modulation of brain pathology effects on cognitive function. Second, longitudinal data of baseline 53 AD spectrum and 34 cognitively unimpaired (CU) participants in the MEMORI dataset were analyzed. CR marker was evaluated for the association with disease conversion rate and clinical progression. Applying our multimodal CR model, this study demonstrates the differential effect of CR on clinical progression according to the disease status and the modulating effect on the relationship between brain pathology and cognition. The proposed marker was associated with years of education and modulated the effect of pathological burden on cognitive performance in the AD spectrum. Longitudinally, higher CR marker was associated with lower disease conversion rate among prodromal AD and CU individuals. Higher CR marker was related to exacerbated cognitive decline in the AD spectrum; however, it was associated with a mitigated decline in CU individuals. These results provide evidence that CR may affect the clinical progression differentially depending on the disease status. [ABSTRACT FROM AUTHOR]

Background: To date, the clinical significance of visually equivocal amyloid positron emission tomography (PET) has not been well established. Objective: We studied the clinical significance of equivocal amyloid PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Methods: Subjects with F-18 florbetapir PET scans at baseline who were followed up for 4 years were selected. Clinical characteristics, imaging biomarkers, cognitive function, and rate of conversion to AD were compared in subjects with visually equivocal findings. Results: Of 249 subjects who completed the follow-up, 153 (61.4%), 20 (8.0%), and 129 (30.5%) were F-18 florbetapir-negative, -equivocal, and -positive, respectively. The mean standardized uptake value ratios (SUVR) of F-18 florbetapir PET were 0.75 ± 0.04, 0.85 ± 0.10, and 1.00 ± 0.09 for each group (p <0.001 between groups), and 15.0%, 70.0%, and 98.7% of patients were quantitatively above the positive threshold. The change in the SUVR of F-18 florbetapir PET was higher in the equivocal (6.09 ± 3.61%, p <0.001) and positive (3.13 ± 4.38%, p <0.001) groups than the negative group (0.88 ± 4.28%). Among the subjects with normal or subjective memory impairment and mild cognitive impairment, 5.3% with negative amyloid PET and 37.5% with positive amyloid PET converted to AD over the 4-year period. None of the equivocal amyloid PET subjects converted to AD during this period. Conclusion: Approximately 8% of subjects from the ADNI cohort showed visually equivocal amyloid PET scans with intermediate load and rapid accumulation of amyloid, but did not convert to AD during the 4-year follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To assess the in vivo whole-brain relationship between uptake of [18F]THK-5351 on PET and cortical atrophy on structural MRI according to the presence and severity of Alzheimer's disease (AD). Materials and methods: Sixty-five participants (21 normal controls, 32 mild cognitive impairment [MCI] subjects, and 12 AD patients) were enrolled from a prospective multicenter clinical trial (NCT02656498). Structural MRI and [18F]THK-5351 PET were performed within a 2-month interval. Cortical volume and standardized uptake value ratios (SUVR) were calculated from MRI and PET images, respectively, for 35 FreeSurfer-derived cortical regions. Pearson's correlation coefficients between SUVR and cortical volume were calculated for the same regions, and correlated regions were compared according to disease severity and β-amyloid PET positivity. Results: No significantly correlated regions were found in the normal controls. Negative correlations between SUVR and cortical volume were found in the MCI and AD groups, mainly in limbic locations in MCI and isocortical locations in AD. The AD group exhibited stronger correlations (r = −0.576–0.781) than the MCI group (r = 0.368–0.571). Hippocampal atrophy did not show any correlation with SUVR in the β-amyloid PET-negative group, but negatively correlated with SUVR (r = −0.494, P =.012) in the β-amyloid PET-positive group. Conclusions: Regional THK-5351 uptake correlated more strongly with cortical atrophy in AD compared with MCI, thereby demonstrating a close relationship between the neuro-pathologic process and cortical atrophy. Hippocampal atrophy was associated with both β-amyloid and THK-5351 uptake, possibly reflecting an interaction between β-amyloid and tau deposition in the neurodegeneration process. [ABSTRACT FROM AUTHOR]

Keywords: draft genome; hybrid assembly; Liza haematocheila; ortholog and phylogenetic analysis; repeat analysis According to the k-mer size estimations, similar genome lengths (698-714 Mb) were observed, and the estimated genome size of I L. haematocheila i was 700 Mb. Therefore, the hybrid assembly approach used in this study was considered effective in reducing the number of contigs and increasing the contig N50 length of the heterozygous diploid genome, by combining Illumina HiSeq short-read and PacBio long-read sequences. Draft genome, hybrid assembly, Liza haematocheila, ortholog and phylogenetic analysis, repeat analysis. [Extracted from the article]

Purpose: Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson's disease (PD) progression and monitoring drug effects. We investigated the longitudinal decline characteristics of striatal [F]FP-CIT uptake in PD. Methods: We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs. Results: Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen. Conclusions: The longitudinal decline of striatal [F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions. [ABSTRACT FROM AUTHOR]

We evaluated cerebellar subregional metabolic alterations in patients with cerebellar ataxia, a representative disease involving the spinocerebellum. We retrospectively analyzed 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images in 44 patients with multiple system atrophy of the cerebellar type (MSA-C), 9 patients with spinocerebellar ataxia (SCA) type 2, and 14 patients with SCA type 6 and compared with 15 patients with crossed cerebellar diaschisis (CCD) and 89 normal controls. Cerebellar subregional metabolism was assessed using 13 cerebellar subregions (bilateral anterior lobes [ANT], superior/mid/inferior posterior lobes [SUPP/MIDP/INFP], dentate nucleus [DN], anterior vermis [ANTV], and superior/inferior posterior vermis [SUPV/INFV]) to determine FDG uptake ratios. MSA-C and SCA type 2 showed severely decreased metabolic ratios in all cerebellar subregions compared to normal controls (ANT, 0.58 ± 0.08 and 0.50 ± 0.06 vs. 0.82 ± 0.07, respectively, p < 0.001). SCA type 6 showed lower metabolic ratios in almost all cerebellar subregions (ANT, 0.57 ± 0.06, p < 0.001) except INFV. Anterior-posterior lobe ratio measurements revealed that SCA type 2 (Right, 0.81 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.83 ± 0.05 vs. 0.88 ± 0.04, p = 0.003) and SCA type 6 (Right, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001) showed preferential hypometabolism in the anterior lobe compared to normal controls, which was not observed in CCD and MSA-C. Asymmetric indices were higher in CCD and MSA-C than in normal controls (p < 0.001), whereas such differences were not found in SCA types 2 and 6. In summary, quantitative analysis of cerebellar subregional metabolism ratios revealed preferential involvement of the anterior lobe, corresponding to the spinocerebellum, in patients with cerebellar ataxia, whereas patients with CCD and MSA-C exhibited more asymmetric hypometabolism in the posterior lobe. [ABSTRACT FROM AUTHOR]

Background: Although cognitive impairment is not a consistent feature of multiple system atrophy (MSA), increasing evidence suggests that cognitive impairment is common in MSA with predominant parkinsonism (MSA-P). It is assumed that the cognitive impairment in MSA-P is caused by the striatal dysfunction and disruption of striatofrontal connections. The aim of this study was to evaluate the relationship between regional glucose metabolism in the frontal cortex and striatum in patients with MSA-P using [18F]FDG brain PET. Methods: Twenty-nine patients with MSA-P and 28 healthy controls underwent [18F]FDG brain PET scan. The [18F]FDG brain PET images were semiquantitatively analyzed on the basis of a template in standard space. The regional glucose metabolism of the cerebral cortex and striatum were compared between MSA-P and healthy control groups. The correlations between age, symptom duration, H&Y stage, UPDRS III score, MMSE score, and glucose metabolism in the cerebellum and striatum to glucose metabolism in the frontal cortex were evaluated by multivariate analysis. Results: The glucose metabolism in the frontal cortex and striatum in MSA-P patients were significantly lower than those in healthy controls. Glucose metabolism in the striatum was the most powerful determinant of glucose metabolism in the frontal cortex in MSA-P. Only age and glucose metabolism in the cerebellum were independent variables affecting the glucose metabolism in the frontal cortex in healthy controls. Conclusion: The decrease in frontal glucose metabolism in MSA-P is related to the decrease in striatal glucose metabolism. This result provided evidence of striatofrontal deafferentiation in patients with MSA-P. [ABSTRACT FROM AUTHOR]

We report a case with altered biodistribution of Tc-dicarboxypropane diphosphonate (Tc-DPD) on whole body bone scan after intravenous iron supplement therapy. A 47-year-old male patient who had recently been detected with a hepatic mass suggestive of hepatocellular carcinoma underwent bone scan as staging work-up before surgery. Bone scan images at 3 h after injection of Tc-DPD demonstrated unusually increased blood pool activities in the heart, liver, and spleen with usual skeletal uptakes. The patient had been treated for severe anemia from hemorrhoid with two intravenous administration of ferric hydroxide carboxymaltose complex at approximately 22 h and 2 h prior to the Tc-DPD injection, which we consider as the most probable cause of altered biodistribution of Tc-DPD. [ABSTRACT FROM AUTHOR]

Purpose: F-FP-CIT [F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane] is useful for detecting striatal dopamine transporter (DAT). Since FP-CIT shows relatively high affinities for DAT and serotonin transporter (SERT), its binding can be influenced by selective serotonin reuptake inhibitors (SSRIs). We aimed to evaluate the effect of SSRIs on the binding of F-FP-CIT. Methods: In our F-FP-CIT positron emission tomography (PET) data pool, images of 24 drug-naive Parkinson's disease (PD) patients (62.6 ± 10.6 years), 111 PD patients taking SSRIs [escitalopram ( n = 19) and fluvoxamine ( n = 20)] or clonazepam ( n = 72), and 10 normal people were reviewed. PET images acquired 3 h after F-FP-CIT injection were analyzed by an automated method using a predefined volume of interest (VOI) set of the striatum (ST), occipital cortex (OC), raphe nuclei (RN), and cerebellar cortex (CB). The uptake ratios (URs) of each VOI to the CB were compared among the groups. Results: The ST/CB URs of all PD groups were significantly lower than that of normal group. When adjusted for drug severity, ST/CB URs were higher in drug-naive group but had no difference among antidepressant groups. Whereas OC/CB URs were not different among groups ( p > 0.05), RN/CB URs were significantly lower in SSRI groups than in non-SSRI groups ( p < 0.001) and showed similar results when adjusted for disease severity. Conclusions: PD patients taking SSRIs showed significantly decreased URs in the RN but not the OC. When adjusted for Hoehn and Yar (HY) score, ST URs were not different among antidepressant groups. This result suggests that the OC may be used as a reference region for the quantification of DAT binding in F-FP-CIT PET images of PD patients taking SSRIs. [ABSTRACT FROM AUTHOR]

A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer's disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aβ positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum. [ABSTRACT FROM AUTHOR]

The recent advance of positron emission tomography (PET) tracers as biomarkers in Alzheimer's disease (AD) provides more insight into pathophysiology, preclinical diagnosis, and further therapeutic strategies. However, synergistic processes or interactions between amyloid and tau deposits are still poorly understood. To better understand their relationship in focal brain changes with clinical phenotypes, we focused on region-specific or atypical AD characterized by focal clinical presentations: Posterior cortical atrophy (PCA) and logopenic variant of primary progressive aphasia (lpvPPA). We compared three different PET images with 18F–THK–5351 (tau), 18F–Florbetaben (amyloid beta, Aβ), and 18F–Fluorodeoxyglucose (glucose metabolism) to investigate potential interactions among pathologies and clinical findings. Whereas the amyloid accumulations were widespread throughout the neocortex, tau retentions and glucose hypometabolism showed focal changes corresponding to the clinical features. The distinctly localized patterns were more prominent in tau PET imaging. These findings suggest that tau pathology correlates more closely to the clinical symptoms and the neurodegenerative processes than Aβ pathology in AD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in reprogramming techniques, a primitive neural stem cell (pNSC) derived from PD patient induced pluripotent stem cells (iPSCs) could be potentially used as a reproducible and reliable experimental system to analyze the effect of the leucine-rich repeat kinase 2 G2019S mutation (LK2GS) in neural cells. Here, we investigated the advantages of such a model system through quantitative proteomic analysis of pNSCs from normal control iPSCs and familial PD patient iPSCs harboring LK2GS. We confirmed that the expression of molecules known to be involved in PD pathogenesis, such as oxidative stress-, cell adhesion-, and cytoskeleton-related proteins, were altered in the LK2GS pNSC. In addition, we showed that down-regulation of Ku80, which was found in the proteomic analysis with LK2GS pNSCs, resulted in apoptosis induced by DNA damage response. Taken together, we suggest that pNSCs from PD iPSCs could provide a reliable and useful model system to study PD. Moreover, the highly expandable pNSC is suitable for multi-omics approaches to understand PD pathologies and discover therapeutic targets for PD. [ABSTRACT FROM AUTHOR]

CXCL8 (interleukin-8, IL-8) is a CXC family chemokine that recruits specific target cells and mediates inflammation and wound healing. This study reports the identification and characterization of two cxcl8 homologs from rock bream, Oplegnathus fasciatus. Investigation of molecular signature, homology, phylogeny, and gene structure suggested that they belonged to lineages 1 (L1) and 3 (L3), and designated Ofcxcl8-L1 and Ofcxcl8-L3. While Ofcxcl8-L1 and Ofcxcl8-L3 revealed quadripartite and tripartite organization, in place of the mammalian ELR (Glu-Leu-Arg) motif, their peptides harbored EMH (Glu-Met-His) and NSH (Asn-Ser-His) motifs, respectively. Transcripts of Ofcxcl8s were constitutively detected by Quantitative Real-Time PCR (qPCR) in 11 tissues examined, however, at different levels. Ofcxcl8-L1 transcript robustly responded to treatments with stimulants, such as flagellin, concanavalin A, lipopolysaccharide, and poly(I:C), and pathogens, including Edwardsiella tarda, Streptococcus iniae, and rock bream iridovirus, when compared with Ofcxcl8-L3 mRNA. The differences in the putative promoter features may partly explain the differential transcriptional modulation of Ofcxcl8s. Purified recombinant OfCXCL8 (rOfCXCL8) proteins were used in in vitro chemotaxis and proliferation assays. Despite the lack of ELR motif, both rOfCXCL8s exhibited leukocyte chemotactic and proliferative functions, where the potency of rOfCXCL8-L1 was robust and significant compared to that of rOfCXCL8-L3. The results, taken together, are indicative of the crucial importance of Ofcxcl8s in inflammatory responses and immunoregulatory roles in rock bream immunity. [ABSTRACT FROM AUTHOR]

Abstract Interleukin-10 (IL-10) is a pleiotropic cytokine involved in the regulation of innate and adaptive immunity. In this study, IL-10 from big-belly seahorse (Hippocampus abdominalis) (HaIL-10) was characterized based on its molecular and functional aspects. The coding sequence of HaIL-10 is 570 bp in length and encodes a 189-amino acid residue protein (calculated molecular weight, 21.89 kDa). The deduced amino acid sequence comprises a typical signal peptide and a mature peptide domain sequence carrying four conserved Cys residues and two additional Cys residues specific to fish. Phylogenetic analysis indicated an evolutionary relationship between HaIL-10 and its counterparts in other vertebrates, with close clustering to the fish-specific homologs. Recombinant HaIL-10 (rHaIL-10) significantly reduced nitric oxide (NO) production by lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells in a concentration-dependent manner but had no effect on cell viability, suggestive of its involvement in immune response. The protein expressions of iNOS and COX-2 were significantly reduced by rHaIL-10 in LPS-induced murine macrophages RAW 264.7 cells. HaIL-10 mRNA expression was observed in all analyzed tissues, with the maximum expression being noted in the kidney and ovary. However, transcriptional levels of HaIL-10 were significantly higher in the blood, gill, and intestine upon in vivo induction with LPS, polyinosinic:polycytidylic acid [poly (I:C)], and Streptococcus iniae. To summarize, our findings help in the improved understanding of the biological functions of HaIL-10 and modulation of HaIL-10 mRNA expression in response to immune stress. Highlights • Identified and characterized interleukin-10 from big-belly seahorse • The HaIL-10 was constitutively expressed in healthy seahorse tissues. • mRNA expression pattern found to be correlated with the immune stresses. • rHaIL-10 reduces NO production in LPS-induced macrophage RAW 264.7 cells. • rHaIL-10 reduces iNOS and COX-2 proteins in LPS-induced macrophage RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

Dendritic-cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) is a C-type lectin that functions as a pattern recognition receptor by recognizing pathogen-associated molecular patterns (PAMPs). It is also involved in various events of the dendritic cell (DC) life cycle, such as DC migration, antigen capture and presentation, and T cell priming. In this study, a DC-SIGN-like gene from the big belly seahorse Hippocampus abdominalis (designated as ShDCS-like ) was identified and molecularly characterized. The putative, complete ORF was found to be 1368 bp in length, encoding a protein of 462 amino acids with a molecular mass of 52.6 kDa and a theoretical isoelectric point of 8.26. The deduced amino acid sequence contains a single carbohydrate recognition domain (CRD), in which six conserved cysteine residues and two Ca 2+ -binding site motifs (QPN, WND) were identified. Based on pairwise sequence analysis, ShDCS-like exhibits the highest amino acid identity (94.6%) and similarity (97.4%) with DC-SIGN-like counterpart from tiger tail seahorse Hippocampus comes. Quantitative real-time PCR revealed that ShDCS-like mRNA is transcribed universally in all tissues examined, but with abundance in kidney and gill tissues. The basal mRNA expression of ShDCS-like was modulated in blood cell, kidney, gill and liver tissues in response to the stimulation of healthy fish with lipopolysaccharides (LPS), Edwardsiella tarda, or Streptococcus iniae . Moreover, recombinant ShDCS-like-CRD domain exhibited detectable agglutination activity against different bacteria. Collectively, these results suggest that ShDCS-like may potentially involve in immune function in big belly seahorses. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose ( 18 F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC)., Materials and Methods: Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage., Results: A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; P < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; P = 0.06), suspicious regional lymph nodes (HR, 1.43; P = 0.02), possible distant metastasis on 18 F-FDG PET/CT (HR, 2.32; P = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; P = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; P = 0.17)., Conclusion: The proposed risk score based on preoperative CA 19-9, CT, and 18 F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC., Competing Interests: Seung Soo Lee, who holds the respective position of Editorial Board Member of the Korean Journal of Radiology, was not involved in the editorial evaluation or decision to publish this article. The remaining author has declared no conflicts of interest., (Copyright © 2024 The Korean Society of Radiology.)

Background: There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels., Methods: Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups., Results: Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT was administered in 166 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response [hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.73-5.58, P <0.001] based on cutoff value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels less than 37 IU/l (median survival; 35.5 vs. 20.9 months, P <0.001) and CA19-9 levels at least 37 IU/l (median survival; 34.3 vs. 17.8 months, P =0.03). In patients suspected to be Lewis antigen negative, the predictive performance of MTV was found to be limited ( P =0.84)., Conclusion: Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

We investigated the longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients in the Alzheimer disease (AD) continuum using 2-(2-([ 18 F]fluoro)pyridin-4-yl)-9 H -pyrrolo[2,3-b:4,5c']dipyridine ([ 18 F]PI-2620) PET. Methods: We prospectively enrolled 52 participants (age, 69.7 ± 8.4 y; 18 men and 34 women): 7 with normal cognition, 28 with mild cognitive impairment, and 17 with AD. They all completed the [ 18 F]PI-2620 and [ 18 F]florbetaben PET, MRI, and neuropsychologic tests at baseline and, excepting the [ 18 F]florbetaben PET, at the 1-y follow-up. Amyloid-β (Aβ) PET images were visually scored as positive (+) or negative (-). Patients on the AD continuum, including Aβ+ mild cognitive impairment and AD, were classified into early-onset (EO+) (<65 y old) or late-onset (LO+) (≥65 y old) groups. [ 18 F]PI-2620 PET SUV ratios (SUVRs) were determined by calculating the cerebral-to-inferior cerebellar ratio. Cortical volumes were calculated using 3-dimensional T1-weighted MRI. The correlation between tau accumulation progression and cognitive decline was also investigated. Results: The global [ 18 F]PI-2620 PET SUVRs were 1.04 ± 0.07 in 15 Aβ- patients, 1.18 ± 0.21 in 20 LO+ patients (age, 76.7 ± 3.8 y), and 1.54 ± 0.38 in 17 EO+ patients (age, 63.4 ± 5.4 y; P < 0.001) at baseline. The global SUVR increased over 1 y by 0.05 ± 0.07 (3.90%) and 0.13 ± 0.22 (8.41%) in the LO+ and EO+ groups, respectively, whereas in the Aβ- groups, it remained unchanged. The EO+ group showed higher global and regional tau deposition than did the Aβ- and LO+ groups ( P < 0.05 for each) and rapid accumulation in Braak stage V (0.15 ± 0.25; 9.10% ± 12.27%; P = 0.016 and 0.008), Braak stage VI (0.08 ± 0.12; 7.16% ± 10.06%; P < 0.006 and 0.005), and global SUVR ( P = 0.013) compared with the Aβ- group. In the EO+ group, the changes in SUVR in Braak stages II-VI were strongly correlated with the baseline and changes in verbal memory ( P < 0.03). The LO+ group showed higher tau accumulation in Braak stage I-IV areas than did the Aβ- group ( P < 0.001 for each). In the LO+ group, the change in SUVR in Braak stages III and IV moderately correlated with the change in attention ( P < 0.05), and the change in SUVR in Braak stages V and VI moderately correlated with the change in visuospatial function ( P < 0.005). Conclusion: These findings suggest that [ 18 F]PI-2620 PET can be a biomarker to provide regional and chronologic information about tau pathology in the AD continuum., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Purpose: Alzheimer's disease (AD) does not always mean amyloid positivity. [ 18 F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [ 18 F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings., Methods: We performed 3.0-T magnetic resonance imaging, [ 18 F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [ 18 F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern., Results: The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [ 18 F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread ( n =10) and extratemporal spread ( n =13). Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [ 18 F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p =0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p =0.006) but not in the intratemporal spread group (-0.5±2.8, p =0.916). The diagnosis remained as AD ( n =5, 50%) or changed to other diagnoses ( n =5, 50%) in the intratemporal group, whereas it remained as AD ( n =8, 61.5%) or changed to frontotemporal dementia ( n =4, 30.8%) and other diagnoses ( n =1, 7.7%) in the extratemporal spread group., Conclusions: Approximately 70% of the patients with amyloid-negative AD showed abnormal [ 18 F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 Korean Neurological Association.)

Purpose: This work aimed to explore in depth the genomic and molecular underpinnings of hepatocellular carcinoma (HCC) with increased 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in PET and to identify therapeutic targets based on this imaging-genomic surrogate., Experimental Design: We used RNA sequencing and whole-exome sequencing data obtained from 117 patients with HCC who underwent hepatic resection with preoperative FDG-PET/CT imaging as a discovery cohort. The primary radiogenomic results were validated with transcriptomes from a second cohort of 81 patients with more advanced tumors. All patients were allocated to an FDG-avid or FDG-non-avid group according to the PET findings. We also screened potential drug candidates targeting FDG-avid HCCs in vitro and in vivo., Results: High FDG avidity conferred worse recurrence-free survival after HCC resection. Whole transcriptome analysis revealed upregulation of mTOR pathway signals in the FDG-avid tumors, together with higher abundance of associated mutations. These clinical and genomic findings were replicated in the validation set. A molecular signature of FDG-avid HCCs identified in the discovery set consistently predicted poor prognoses in the public-access datasets of two cohorts. Treatment with an mTOR inhibitor resulted in decreased FDG uptake followed by effective tumor control in both the hyperglycolytic HCC cell lines and xenograft mouse models., Conclusions: Our PET-based radiogenomic analysis indicates that mTOR pathway genes are markedly activated and altered in HCCs with high FDG retention. This nuclear imaging biomarker may stimulate umbrella trials and tailored treatments in precision care of patients with HCC., (©2022 American Association for Cancer Research.)

Purpose: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18 F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer's disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ-) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer's disease pathophysiology. Accordingly, we investigated associations between 18 F-THK5351 PET positivity and cognitive decline among Aβ- aMCI patients., Materials and Methods: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18 F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18 F-THK5351 PET positivity on cognitive prognosis among Aβ- aMCI patients., Results: Among the 25 Aβ- aMCI patients, 10 (40.0%) were 18 F-THK5351 positive. The patients in the 18 F-THK5351-positive group were older than those in the 18 F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p <0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18 F-THK5351-positive group deteriorated at a faster rate than those of the 18 F-THK5351-negative group (B=0.003, p =0.033)., Conclusion: The results of the present study suggest that increased 18 F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ- aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498)., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Objectives: In this study, we aimed to analyze patient mortality rate after non-operative treatment of hip fractures to determine the distribution of causes of death and to compare factors affecting mortality., Patients and Methods: Between January 2013 and March 2019, a total of 93 patients (17 males, 76 females; mean age: 86.0±7.4 years; range, 64 to 98 years) who had hip fractures and were treated non-operatively were analyzed retrospectively. Survival, date of death, and cause of death were collected and analyzed. Baseline demographics, pre-trauma ambulation, pre- and post-trauma residence status, American Society of Anesthesiologists Physical Status (ASA PS) classification, and Parker's mobility score were compared with one-year mortality rates., Results: The mean follow-up of survivors was 16.1±11.9 (range, 6.3 to 79.6) months. The mean survival of non-survivors was 4.9±6.1 (range, 0.007 to 27.3) months. The 3-, 6-, 12-, and 24-month mortality rates were 40.9%, 53.3%, 74.4%, and 87.5%, respectively. Respiratory diseases (33.3%) and cardiovascular diseases (13.6%) were the main causes of death among the patients. There was no statistically significant difference between the patients' age, sex, fracture site, pre-trauma ambulation, pre- and post-trauma residence status, ASA PS classification, Parker's mobility score, and one-year mortality., Conclusion: A significant number of patients are still treated non-operatively after hip fractures, and they have a high mortality rate. Efforts and research are needed to reduce mortality and improve the quality of life.

Background: The purpose of this study was to investigate the characteristics of women with subsequent distal radius fracture (DRF) and to compare bone fragility variables in women with initial and subsequent DRF., Methods: We enrolled 227 women who experienced DRF (203 women with initial DRF and 24 women with subsequent DRF) between September 2016 and April 2019. We compared demographic characteristics and bone fragility variables, including bone mineral density, trabecular bone score, hip geometry, bicortical thickness of the distal radius, and fracture risk assessment tool (FRAX) scores between the 2 groups. To reduce bias, patients with subsequent DRF were propensity score-matched in a 1:2 manner with patients affected by initial DRF, and additional comparisons were performed., Results: Patients in the subsequent DRF group were older than those in the initial DRF group, but this difference was not significant (P=0.091). The proportion of patients receiving treatment with osteoporosis medication was significantly higher in the subsequent DRF group (41.7% vs. 19.2%, P=0.011). Bone fragility variables did not differ significantly between the 2 groups. However, the ten-year probability of major osteoporotic fractures based on FRAX scores was significantly higher in patients with subsequent DRF (7.5% vs. 10.8%, P<0.001). Similar results were observed when comparing the propensity score-matched initial and subsequent DRF groups., Conclusions: These findings suggest that the occurrence of subsequent DRF after initial DRF can be attributed to multiple factors rather than bone fragility alone. Systematic and multidisciplinary management would be helpful in preventing the occurrence of subsequent DRF after the initial DRF.

Abstract: It remains uncertain whether statin/ezetimibe combination therapy serves as a useful and equivalent alternative to statin monotherapy for reducing atherosclerotic plaque inflammation. The aim of the present study was to compare the effects of statin/ezetimibe combination therapy and statin monotherapy on carotid atherosclerotic plaque inflammation using 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) imaging. Data were pooled from 2 clinical trials that used serial 18FDG PET/CT examination to investigate the effects of cholesterol-lowering therapy on carotid atherosclerotic plaque inflammation. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS) at 6-month follow-up. Baseline characteristics were largely similar between the 2 groups. At the 6-month follow-up, the MDS TBR of the index vessel significantly decreased in both groups. The percent change in the MDS TBR of the index vessel (primary outcome) did not differ significantly between the 2 groups (-8.41 ± 15.9% vs -8.08 ± 17.0%, respectively, P = .936). Likewise, the percent change in the whole vessel TBR of the index vessel did not differ significantly between the 2 groups. There were significant decreases in total and LDL cholesterol levels in both groups at follow-up (P < .001). There were no significant correlations between the percent changes in MDS TBR of the index vessel, changes in the lipid, and high-sensitive C-reactive protein levels. The reduction in carotid atherosclerotic plaque inflammation by statin/ezetimibe combination therapy was equivalent to that by the statin monotherapy., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

We evaluated cerebellar subregional metabolic alterations in patients with cerebellar ataxia, a representative disease involving the spinocerebellum. We retrospectively analyzed 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images in 44 patients with multiple system atrophy of the cerebellar type (MSA-C), 9 patients with spinocerebellar ataxia (SCA) type 2, and 14 patients with SCA type 6 and compared with 15 patients with crossed cerebellar diaschisis (CCD) and 89 normal controls. Cerebellar subregional metabolism was assessed using 13 cerebellar subregions (bilateral anterior lobes [ANT], superior/mid/inferior posterior lobes [SUPP/MIDP/INFP], dentate nucleus [DN], anterior vermis [ANTV], and superior/inferior posterior vermis [SUPV/INFV]) to determine FDG uptake ratios. MSA-C and SCA type 2 showed severely decreased metabolic ratios in all cerebellar subregions compared to normal controls (ANT, 0.58 ± 0.08 and 0.50 ± 0.06 vs. 0.82 ± 0.07, respectively, p < 0.001). SCA type 6 showed lower metabolic ratios in almost all cerebellar subregions (ANT, 0.57 ± 0.06, p < 0.001) except INFV. Anterior-posterior lobe ratio measurements revealed that SCA type 2 (Right, 0.81 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.83 ± 0.05 vs. 0.88 ± 0.04, p = 0.003) and SCA type 6 (Right, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001) showed preferential hypometabolism in the anterior lobe compared to normal controls, which was not observed in CCD and MSA-C. Asymmetric indices were higher in CCD and MSA-C than in normal controls (p < 0.001), whereas such differences were not found in SCA types 2 and 6. In summary, quantitative analysis of cerebellar subregional metabolism ratios revealed preferential involvement of the anterior lobe, corresponding to the spinocerebellum, in patients with cerebellar ataxia, whereas patients with CCD and MSA-C exhibited more asymmetric hypometabolism in the posterior lobe.