Effect of malnutrition on FDG PET

Objective 18F-FDG PET/CT is a hybrid imaging method widely used as a useful, noninvasive imaging modality for evaluating various neoplastic diseases. When assessing the tumor uptake, the liver and the mediastinal blood pool are often used as a reference region. In daily clinical practice, the 18F-FDG uptake in the liver sometimes appears to decrease on PET images of patients with malnutrition. The purpose of this study was to investigate whether or not the liver 18F-FDG uptake is decreased in patients with malnutrition. Methods We retrospectively analyzed 246 patients who underwent 18F-FDG PET/CT from January 2018 to June 2018 and whose blood serum albumin was measured within 1 month of PET/CT. We compared the liver uptake and mediastinal blood uptake of patients with low serum albumin level (< 4.0 g/dl) and hypoalbuminemia (< 3.5 g/dl) with those with a normal serum albumin level (≥ 4.0 g/dl). Correlations between the liver and mediastinal blood uptake and the serum albumin level were also calculated. Results The maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) of the liver in 117 patients with low serum albumin were 3.1 ± 0.5 and 2.3 ± 0.3, respectively, while they were 2.9 ± 0.4, 2.0 ± 0.3 in 29 patients with hypoalbuminemia; these values were all significantly lower than the respective ones (3.4 ± 0.5, 2.5 ± 0.4) in 129 patients with normal serum albumin (all p < 0.001). The SUVmean of the mediastinal blood uptake in patients with hypoalbuminemia and normal serum albumin were 1.6 ± 0.2 and 1.7 ± 0.3, respectively (p = 0.053). The serum albumin level demonstrated a significantly positive, moderate correlation with the liver SUVmean, showing a regression line of y = 0.31x + 1.1 (r = 0.41, p < 0.001). Conclusion The liver 18F-FDG uptake tended to decrease in patients with hypoalbuminemia. In the patients with malnutrition, the mediastinal blood pool may be more stable reference than the liver for evaluating the tumor activity because hypoalbuminemia is considered to less strongly influence the mediastinal blood pool than that in the liver

Depletion of perivascular macrophages delays ALS disease progression by ameliorating blood-spinal cord barrier impairment in SOD1G93A mice

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease in which non-cell-autonomous processes have been proposed as its cause. Non-neuronal cells that constitute the environment around motor neurons are known to mediate the pathogenesis of ALS. Perivascular macrophages (PVM) are immune cells that reside between the blood vessels of the central nervous system and the brain parenchyma; PVM are components of the neurovascular unit and regulate the integrity of the blood-spinal cord barrier (BSCB). However, it is not known whether regulation of BSCB function by PVM is involved in the pathogenesis of ALS. Here, we used SOD1G93A mice to investigate whether PVM is involved in the pathogenesis of ALS. Immunostaining revealed that the number of PVM was increased during the disease progression of ALS in the spinal cord. We also found that both anti-inflammatory Lyve1+ PVM and pro-inflammatory MHCII+ PVM subtypes were increased in SOD1G93A mice, and that subtype heterogeneity was shifted toward MHCII+ PVM compared to wild-type (WT) mice. Then we depleted PVM selectively and continuously in SOD1G93A mice by repeated injection of clodronate liposomes into the cerebrospinal fluid and assessed motor neuron number, neurological score, and survival. Results showed that PVM depletion prevented the loss of motoneurons, slowed disease progression, and prolonged survival. Further histological analysis showed that PVM depletion prevents BSCB collapse by ameliorating the reduction of extracellular matrix proteins necessary for the maintenance of barrier function. These results indicate that PVM are involved in the pathogenesis of ALS, as PVM degrades the extracellular matrix and reduces BSCB function, which may affect motor neuron loss and disease progression. Targeting PVM interventions may represent a novel ALS therapeutic strategy

Utility of Superb Microvascular Imaging in the Assessment of Foot Perfusion in Patients with Critical Limb Ischemia

(1) Background: Although the ankle–brachial index (ABI) and skin perfusion pressure (SPP) are commonly used to evaluate the peripheral circulation in critical limb ischemia (CLI), they often cannot be performed on sore areas. We investigated the utility of superb microvascular imaging (SMI) for assessing foot perfusion in CLI patients.(2) Methods: We measured the SMI-based vascular index (SMI-VI) at six sites in the foot before and after endovascular treatment (EVT) in 50 patients with CLI who underwent EVT of the superficial femoral artery and compared the results with SPP values and the ABI.(3) Results: SMI visualized foot perfusion in all subjects in accordance with the angiosome, including the toe areas, while the ABI was unmeasurable in three patients on hemodialysis and SPP failed in four patients. SMI-VI values were significantly lower in the CLI group than in controls, and the plantar SMI-VI had the highest diagnostic performance for CLI (sensitivity 88.6%, specificity 95.6%). After EVT, the increase in the SMI-VI was positively correlated with the increase in SPP but not that in the ABI, implying that the SMI-VI reflects foot microcirculation. (4) Conclusions: SMI enables the visualization and quantification of foot microcirculation based on the angiosome. SMI has high utility as a tool for assessing foot perfusion in CLI

Semiquantitative assessment of FDG uptake in primary tumours

Objective: To semiquantitatively estimate fluorine-18-fluorodeoxyglucose (FDG) uptake in primary lung cancer cells using dynamic and dual-time-point (DTP) positron emission tomography/computed tomography (PET/CT) to obtain a diagnostic index for lymph node (LN) metastasis. Methods: Forty-five patients with lung cancer underwent dynamic and DTP PET/CT examinations. All primary lesions and LN metastases were evaluated pathologically. At each time phase, we assessed the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the primary tumours. We investigated the relationship between semiquantitative index and the presence of LN metastasis for each case and for all cases satisfying indications for segmentectomy. In cases with LN metastasis, we assessed the SUVmax of pathologically proven metastatic LNs and non-metastatic LNs in each dynamic phase for evaluating temporal change. Results: Among 45 patients, 15 had 17 LN metastasis. SUVmax, MTV, and TLG of primary tumours at each time phase were significantly associated with LN metastasis (p < 0.05). In receiver operating characteristic analysis, dynamic second and third phases showed high diagnostic ability for LN metastasis. The temporal change in SUVmax in the dynamic phase between primary tumours and metastatic LNs were significantly different (p = 0.065). The temporal change in SUVmax was significantly lower in non-metastatic LNs than in primary tumours and metastatic LNs (p < 0.0001). Conclusions: Semiquantitative assessment of FDG uptake in dynamic second and third phases and the assessment of temporal changes in SUVmax on dynamic PET/CT scans were important predictors in diagnosing LN metastasis

<実践研究>大学体育水球授業モデルの開発 : 水球を教材とした大学体育授業の実践に関する効果と課題の検討を通して

The water polo is thought to be an ideal teaching material to master swimming skills and ball game skills at once for students, but in fact there are very few physical education classes in which the water polo is teaching at Japanese universities. Therefore, the aim of this study was to design teaching plans using the water polo for physical education classes in the university, and to verify the educational effects and problems of this class. The lesson was held in an indoor 50m swimming pool at University of Tsukuba, and a total of 6 students participated the class. The two-day water polo intensive program was consisted of an actual training in the water and a classroom lecture. After the two-day water polo intensive program, participants’ skills relevant to the water polo, in particular treading water, dribbling the ball and reciprocate swimming were improved. According to the students’ description, they thought that they were able to improve their basic techniques about the water polo, but they felt a difficulty to use the basic techniques during the actual game. An overall evaluation by the students about the intensive course was quite high and the two-day program was too short to learn. From the above, it is suggested that water polo is a good material for learning swimming skills but also water safety and communication in the water. However the water polo is so tough the class should be held once a week like another classes. Based on these effects and problems, new teaching plan for water polo in the university was presented

ACPA-negative RA consists of two genetically distinct subsets based on RF positivity in Japanese.

HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10(-6) and 0.0011, OR: 1.57 (1.28-1.91) and 1.37 (1.13-1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21-1.89) and 3.08 (1.68-5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote

Site-specific isotope labeling of long RNA for structural and mechanistic studies

A site-specific isotope labeling technique of long RNA molecules was established. This technique is comprised of two simple enzymatic reactions, namely a guanosine transfer reaction of group I self-splicing introns and a ligation with T4 DNA ligase. The trans-acting group I self-splicing intron with its external cofactor, ‘isotopically labeled guanosine 5′-monophosphate’ (5′-GMP), steadily gave a 5′-residue-labeled RNA fragment. This key reaction, in combination with a ligation of 5′-remainder non-labeled sequence, allowed us to prepare a site-specifically labeled RNA molecule in a high yield, and its production was confirmed with 15N NMR spectroscopy. Such a site-specifically labeled RNA molecule can be used to detect a molecular interaction and to probe chemical features of catalytically/structurally important residues with NMR spectroscopy and possibly Raman spectroscopy and mass spectrometry

Observation of Mixing-induced CP Violation in the Neutral B Meson System

This report describes an observation of mixing-induced CP violation and a measurement of the CP violation parameter, sin(2phi_1), with the Belle detector at the KEKB asymmetric e+e- collider. Using a data sample of 29.1 fb-1 recorded on the Upsilon(4S) resonance that contains 31.3 million BBbar pairs, we reconstruct decays of neutral B mesons to the following CP eigenstates: J/psi K_S^0, psi(2S) K_S^0, chi_c1 K_S^0, eta_c K_S^0, J/psi K_L^0 and J/psi K^*0. The flavor of the accompanying B meson is identified by combining information from primary and secondary leptons, K+/- mesons, lambda baryons, slow and fast pions. The proper-time interval between the two B meson decays is determined from the distance between the two decay vertices measured with a silicon vertex detector. The result sin(2phi_1) = 0.99 +/- 0.14(stat) +/- 0.06(syst) is obtained by applying a maximum likelihood fit to the 1137 candidate events. We conclude that there is large CP violation in the neutral B meson system. A zero value for sin(2phi_1) is ruled out by more than six standard deviations.Comment: 25 pages, 16 figures, accepted for publication in Physical Review