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Aims: Several diet quality indicators have been developed primarily for cardiovascular disease (CVD) prevention in Western countries. However, those previous indicators are complicated and less feasible in clinical and health-promoting settings. Therefore, we aimed to develop a concise dietary risk score for CVD prevention in Japanese., Methods: Using the self-administered food frequency questionnaire with 35 food items, we developed a concise healthy diet score (cHDS) ranging from 0 to 5 points. We examined the association of cHDS with risks of all-cause and cause-specific mortality among 23,115 men and 35,557 women who were free of CVD and cancer., Results: During 19.2 years of median follow-up, 6,291 men and 5,365 women died. In men, the multivariable hazard ratios (95% confidence intervals) for the highest cHDS (5 points) compared to the lowest (0-1 points) were 0.74 (0.60-0.91, P-trend=0.008) for CVD and 0.86 (0.77-0.95, P-trend=0.05) for all causes. No significant associations were found for stroke, coronary heart disease, and other causes in men. The corresponding hazard ratio in women was 0.65 (0.52-0.81, P-trend＜0.001) for CVD, 0.63 (0.45-0.88, P-trend＜0.001) for stroke, 0.48 (0.30-0.78, P-trend=0.008) for coronary heart disease, 0.67 (0.54-0.84, P-trend＜0.001) for other causes, and 0.75 (0.66-0.85, P-trend＜0.001) for all causes., Conclusion: We developed a concise diet quality score named cHDS in the Japanese population and found the inverse association of cHDS with mortality from CVD and all causes for both men and women.

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tuyishime, Spreng, Hueber, Nohara, Goodman, Chan, Barfield, Beck, Jha, Asdell, Wiehe, He, Easterhoff, Conley, Hoxie, Gurley, Jones, Adhikary, Villinger, Thomas, Denny, Moody, Tomaras, Pollara, Reeves and Ferrari.)

An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T cell help and improve antibody production against HIV-1. To test this, we developed an innovative conjugate vaccine regimen that used a modified vaccinia virus Ankara (MVA) co-expressing HIV-1 envelope (Env) and the hepatitis B virus surface antigen (HBsAg) as a prime, followed by two Env-HBsAg conjugate protein boosts. We compared the immunogenicity of this conjugate regimen to matched HIV-1 Env-only vaccines in two groups of 5 juvenile rhesus macaques previously immunized with hepatitis B vaccines in infancy. We found expansion of both HIV-1 and HBsAg-specific circulating T follicular helper cells and elevated serum levels of CXCL13, a marker for germinal center activity, after boosting with HBsAg-Env conjugate antigens in comparison to Env alone. The conjugate vaccine elicited higher levels of antibodies binding to select HIV Env antigens, but we did not observe significant improvement in antibody functionality, durability, maturation, or B cell clonal expansion. These data suggests that conjugate vaccination can engage both HIV-1 Env and HBsAg specific T cell help and modify antibody responses at early time points, but more research is needed to understand how to leverage this strategy to improve the durability and efficacy of next-generation HIV vaccines., (© 2023. The Author(s).)

Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) is effective at limiting seeding of the HIV viral reservoir, but little is known about how the resultant decreased antigen load affects long-term Ab development after ART. We report here that Env-specific plasma antibody (Ab) levels and Ab-dependent cellular cytotoxicity (ADCC) increased during the first 24 weeks of ART and correlated with Ab levels persisting after 48 weeks of ART. Participants treated in AHI stage 1 had lower Env-specific Ab levels and ADCC activity on ART than did those treated later. Importantly, participants who initiated ART after peak viremia in AHI developed elevated cross-clade ADCC responses that were detectable 1 year after ART initiation, even though clinically undetectable viremia was reached by 24 weeks. These data suggest that there is more germinal center (GC) activity in the later stages of AHI and that Ab development continues in the absence of detectable viremia during the first year of suppressive ART. The development of therapeutic interventions that can enhance earlier development of GCs in AHI and Abs after ART initiation could provide important protection against the viral reservoir that is seeded in individuals treated early in the disease.

Amyloid formation is involved in a wide range of neurodegenerative diseases including Alzheimer's and prion diseases. Structural understanding of the amyloid is critical to delineate the mechanism of aggregation and its pathological spreading. Site-directed spin labelling has emerged as a powerful structural tool in the studies of amyloid structures and provided structural evidence for the parallel in-register β-sheet structure for a wide range of amyloid proteins. It is generally accepted that spin labelling does not disrupt the structure of the amyloid fibrils, the end product of protein aggregation. The effect on the rate of protein aggregation, however, has not been well characterized. Here, we employed a scanning mutagenesis approach to study the effect of spin labelling on the aggregation rate of 79 spin-labelled variants of the Ure2 prion domain. The aggregation of Ure2 protein is the basis of yeast prion [URE3]. We found that all spin-labelled Ure2 mutants aggregated within the experimental timeframe of 15 to 40 h. Among the 79 spin-labelled positions, only five residue sites (N23, N27, S33, I35 and G42) showed a dramatic delay in the aggregation rate as a result of spin labelling. These positions may be important for fibril nucleation, a rate-limiting step in aggregation. Importantly, spin labelling at most of the sites had a muted effect on Ure2 aggregation kinetics, showing a general tolerance of spin labelling in protein aggregation studies., (© 2021 The Authors.)

A 70-year-old woman had spontaneous resolution of an embolism in her right middle cerebral artery (MCA) (day 1); another embolism occurred in her left MCA (day 3), which was promptly removed. On day 5, F-FDG PET/CT performed for staging mediastinal lymphoma showed marked FDG accumulation in the left MCA territory, whereas a defect was seen in the right insular region. Eventually, bilateral lesions developed irreversible infarction. Anaerobic metabolism and/or inflammation in acute-phase infarction were the supposed mechanism for the increased accumulation of FDG in her left MCA territory.

Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution of regulatory and adaptive roles. Animal models, particularly non-human primate (NHP) models, are critical for characterizing NK cell biology in disease and under homeostatic conditions. In HIV infection, NK cells mediate multiple antiviral functions via upregulation of activating receptors, inflammatory cytokine secretion, and antibody dependent cell cytotoxicity through antibody Fc-FcR interaction and others. However, HIV infection can also reciprocally modulate NK cells directly or indirectly, leading to impaired/ineffective NK cell responses. In this review, we will describe multiple aspects of NK cell biology in HIV/SIV infections and their association with viral control and disease progression, and how NHP models were critical in detailing each finding. Further, we will discuss the effect of NK cell depletion in SIV-infected NHP and the characteristics of newly described memory NK cells in NHP models and different mouse strains. Overall, we propose that the role of NK cells in controlling viral infections remains incompletely understood and that NHP models are indispensable in order to efficiently address these deficits.

Fully absorption coefficient corrected Raman spectra were obtained in La2-xSrxCuO4. The B1g spectra have a Fleury-Loudon type two-magnon peak (resonant term) whose energy decreases from 3180 cm(-1) (394 meV) to 440 cm(-1) (55 meV) on increasing the carrier density from x = 0 to 0.25, while the B2g spectra have a 1000-3500 cm(-1) (124-434 meV) hump (hill) whose lower-edge energy increases from x = 0 to 0.115 and then stays constant to x = 0.25. The B2g hump is assigned to the electronic scattering (non-resonant term) of the spectral function with magnetic self-energy. The completely different carrier density dependence arises from anisotropic magnetic excitations of spin-charge stripes. The B1g spectra were assigned to the sum of k ∥  and k⊥ stripe excitations and the B2g spectra to k⊥ stripe excitations according to the calculation by Seibold and Lorenzana (2006 Phys. Rev. B 73 144515). The k ∥  and k⊥ stripe excitations in fluctuating spin-charge stripes were separately detected for the first time. The appearance of only k⊥ stripe excitations in the electronic scattering arises from the charge hopping perpendicular to the stripe. This is the same direction as the Burgers vector of the edge dislocation in metal. The successive charge hopping in the Burgers vector direction across the charge stripes may cause Cooper pairs as predicted by Zaanen et al (2004 Ann. Phys. 310 181). Indeed, this is supported by the experimental fact that the superconducting coherent length coincides with the inter-charge stripe distance in the wide carrier density range. The one-directional charge hopping perpendicular to the stripe causes the flat Fermi surface and the pseudogap near (π,0) and (0,π), but the states around (π/2,π/2) cannot be produced. The low-energy Raman scattering disclosed that the electronic states at the Fermi arc around (π/2,π/2) are coupled to the A1g soft phonon of the tetragonal-orthorhombic phase transition. This suggests that the Fermi arc is produced by the electron-phonon interaction. All the present Raman data suggest that Cooper pairs are formed at moving edge dislocations of dynamical charge stripes.

Objectives: Although positron emission tomography (PET) using [(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is established as one of the first-choice imaging modalities in the diagnosis of chest malignancies, there are several problems to solve in clinical practice, such as false positive uptake in inflammatory diseases. The aim of this study was to evaluate the clinical usefulness of an amino acid tracer, α-[N-methyl-(11)C]-methylaminoisobutyric acid ((11)C-MeAIB), in the diagnosis of chest malignancies, in combination with (18)F-FDG., Setting: Fifty-nine cases (57 patients, 66 ± 12 years old) who consulted to our institution for the wish to receive differential diagnosis of chest diseases were included. Purpose of the studies were as follows: differential diagnosis of newly developed lung nodules, n = 22; newly developed mediastinal lesions, n = 20; and both, n = 17 (including lung cancer: n = 19, lymphoma: n = 1, other cancers: n = 2, sarcoidosis: n = 15, non-specific inflammation: n = 18, other inflammatory: n = 4, respectively). Whole-body static PET or PET/CT scan was performed 20 and 50 min after the IV injection of (11)C-MeAIB and (18)F-FDG, respectively., Results: (11)C-MeAIB uptake of malignant and benign lesions was statistically different both in pulmonary nodules (p < 0.005) and in mediastinal lesions (p < 0.0005). In visual differential diagnosis, (11)C-MeAIB showed higher results (specificity: 73 %, accuracy: 81 %), compared to those in (18)F-FDG (60, 73 %, respectively). In cases of sarcoidosis, (11)C-MeAIB showed higher specificity (80 %) with lower uptake (1.8 ± 0.7) in contrast to the lower specificity (60 %) with higher uptake of (18)F-FDG (7.3 ± 4.5)., Conclusions: (11)C-MeAIB PET/CT was useful in the differential diagnosis of pulmonary and mediastinal mass lesions found on CT. (11)C-MeAIB PET or PET/CT showed higher specificity than that of (18)F-FDG PET/CT in differentiating between benign and malignant disease. Our data suggest that the combination of (18)F-FDG and (11)C-MeAIB may improve the evaluation of chest lesions, when CT and (18)F-FDG PET/CT are equivocal.

In a strongly correlated electron system, the single-particle spectral function changes into a coherent peak and incoherent humps which extend over 1 eV. The incoherent parts lose the symmetry and k dependence, so that the Raman spectra with different symmetries become identical and they are expressed by the optical conductivity. We found that the B1g and B2g spectra in La(2-x)Sr(x)CuO4 become identical above 2000 cm(-1) in the underdoped phase, if Fleury-Loudon type B1g two-magnon scattering is removed. The first Raman susceptibility moment correlates with the generalized optical conductivity moment. The good correlation arises from the incoherent states of a hump from 1000 to 4000 cm(-1). The hump is the only structure of the incoherent electronic states in the mid-infrared absorption spectra below 1.4 eV at low carrier densities. The energy is twice the separated dispersion segments of the spin wave in the k(perpendicular) stripe direction. The incoherent state is formed by the magnetic excitations created by the hole hopping in the antiferromagnetic spin stripes in the real space picture.

A 58-year-old man visited our department regarding a growing ground-glass opacity (GGO) on chest CT. He underwent video-assisted thoracic surgery, because a malignancy such as bronchioloalveolar adenocarcinoma was suspected. However, histopathologic examination revealed pulmonary alveolar proteinosis (PAP). A chest X-ray film of PAP usually shows bilateral interstitial and/or alveolar shadows in a "butterfly pattern", while chest CT usually shows thickened interlobular septa and intralobular structures, referred to as a "crazy-paving appearance". The present case presented solitary localized GGO growing in a subpleural area which was thought to be a rare type of early PAP.

A 69-year-old man was admitted complaining of bloody sputum. A chest X-ray and CT revealed no abnormal findings, but bronchoscopy revealed a squamous cell carcinoma nodular lesion in the bifurcation between the left B(1+2)a and B(1+2)b. After two courses of chemotherapy (CBDCA + PAC), the nodular lesion disappeared. Another nodular squamous cell carcinoma grew in the orifice of the left B(1+2) nine months later, but this time chemotherapy was ineffective. The nodular tumor was cauterized twice with argon plasma coagulation, and no recurrence appeared for twenty-six months.

We describe the successful extraction from an airway of foreign bodies metal nails in three cases. They were all carpenters, and often held nails between their lips. Case 1: a 72-year-old man had aspirated a nail three months earlier, but did not seek medical assistance at the time. A chest X-ray film and CT examination revealed a nail in the peripheral S7 region of the right lower lobe. The nail could not be extracted with forceps via bronchoscopy, so video-assisted thoracic surgery was performed. During surgery, the nail moved to the truncus intermedius, then it was extracted using bronchoscopy forceps. The extracted nail was rust-proof, and no rust was observed. Case 2 : a 76-year-old man visited our hospital with a history bloody sputum with a slightly dry cough for two months. A chest X-ray film showed a nail in the right hilum. Bronchoscopy revealed the nail covered with mucinous secretion in the right B7, and it was extracted by forceps. It was a rust-proof type nail, and no granulation tissue was observed in the bronchus. Case 3: a 74-year-old man visited our hospital because of dry cough for two months. A chest X-ray revealed a nail in the right hilus and bronchoscopy showed the nail was buried in reactive granulation tissue in the right middle lobe bronchus and could not be observed from the surface. Tranilast (n-[3,4-dimethoxycinnamoyl] anthranilic acid) at 300 mg/day and Methylprednisolone at 250 mg/day were prescribed for 4 days, followed by a reduction of the corticosteroid to 40 mg/day for 3 days. Seven days later, the granulation tissue and mucosal edema had diminished, and the nail was successfully extracted. The extracted nail was not rust-proof and had swollen with rust. These nails were found a few months after aspiration. The reason why these were not defected was possibly that the long and narrow shape did not obstruct the segmental bronchus and the symptoms can be less severe compared with other foreign bodies. The rust-proof nails were covered with mucinous secretion, but the nail without coating had rusted and caused reactive granulation tissue and swelling observed. Corticosteroid and Tranilast are thought to be effective in reducing such granulation tissue in airways.

We present a case of intrabronchial foreign body buried in granulation tissue, which was successfully extracted administrating tranilast (n-[3,4-dimethoxycinnamoyl] anthranilic acid), suppressing collagen synthesis by fibroblasts in keloid and hypertrophic scars, and corticosteroid. Bronchoscopy of a 74-year-old man showed the nail was buried in reactive granulation tissue and could not be observed from the surface. Tranilast at 300 mg/day and methylprednisolone at 250 mg/day were prescribed for 4 days, followed by a reduction of the corticosteroid to 40 mg/day for 3 days. Seven days later, the granulation tissue and mucosal edema were diminished, and the nail was successfully extracted.

A 75-year-old man underwent right hemi-colectomy in 2003. After recurrence in November, 2005, he had been given CDDP and TS-1. He had complained of cough with white sputum and fever from the end of October, 2006, however, antibiotics did not improve his symptoms. The chest CT showed diffuse ground glass opacities (GGO) in bilateral lung fields. Steroid treatment improved his physical condition and chest x-ray. Drug-induced pneumonia caused by TS-1 was diagnosed data from a drug lymphocyte stimulation test (DLST). Drug induced interstitial pneumonia can therefore occur after long-term administration.

A 72-year-old woman was admitted to our hospital with exacerbation of dyspnea. She had a history of rheumatoid arthritis (RA) for 26 years, and had been taking methotrexate and prednisolone. Chest radiograph and chest CT revealed marked mediastinal and right axillary lymph node swelling, interstitial shadows and bilateral pleural effusion. A biopsy of the right axillary lymph node for histopathological examination revealed diffuse large B cell lymphoma. The patient achieved complete remission, following 7 cycles of chemotherapy (R-EPOCH). As RA is associated with an increased risk of developing lymphoma, malignant lymphoma must be considered as a possible cause of the mediastinal swelling in a patient with RA.

We report two cases of lung abscesses treated with percutaneous drainage. A 69-year-old man with diabetes mellitus was admitted to our hospital because of fever. Chest radiograph and chest CT scan demonstrated a lung abscess adjacent to the chest wall in right S10. Antibiotics did not achieve an adequate response. A drainage catheter was inserted percutaneously. We washed the abscess cavity daily using 1% povidone iodine saline. There was a clear improvement on the chest radiograph. A 74-year-old man with cerebral infarct was admitted to our hospital because of persistent cough and fever. Chest radiograph and chest CT scan demonstrated a lung abscess adjacent to the chest wall in left S10. Antibiotics did not achieve an adequate response. A drainage catheter was inserted percutaneously. We washed the abscess cavity daily using 1% povidone iodine saline. There was a clear improvement on the chest radiograph. We think that percutaneous drainage is a very useful method to treat lung abscesses in which antibiotics do not achieve an adequate response.

Some antidepressants, as well as antiepileptics, are effective for treating pain of varying etiology. The present study was designed to characterize the antinociceptive effects of imipramine, a tricyclic antidepressant, fluvoxamine, a selective serotonin reuptake inhibitor, milnacipran, a serotonin noradrenaline reuptake inhibitor, and carbamazepine, an antiepileptic drug, using the acetic acid-induced writhing test in mice. Imipramine (1.25-10 mg/kg, i.p.), fluvoxamine (5-40 mg/kg, i.p.) and milnacipran (2.5-20 mg/kg, i.p.) all dose-dependently and significantly reduced the number of writhes induced by the injection of acetic acid (0.8% (v/v)), although the maximal effect of milnacipran was weaker than those of imipramine and fluvoxamine. Similarly, carbamazepine (5-20 mg/kg, i.p.) also showed a dose-dependent and significant antinociceptive effect. In combination studies, the co-administration of a sub-effective dose of carbamazepine (5 mg/kg, i.p.) with imipramine (1.25 and 2.5 mg/kg, i.p.), fluvoxamine (10 mg/kg, i.p.) or milnacipran (1.25 and 2.5 mg/kg, i.p.) significantly reduced the number of writhes. Additionally, the hole-board test revealed that the medications with significant antinociceptive effects barely produced changes in motor activity that could possibly affect writhing behavior. Thus, the present study demonstrated that the antinociceptive effect of carbamazepine is enhanced by combination with imipramine, fluvoxamine and milnacipran. Therefore, the combined therapy using antidepressants and carbamazepine may be useful clinically for the control of pain.

Optical conductivity measurements on the organic metal theta-(BEDT-TTF)2I3 revealed that the system crosses over rapidly from a coherent quasiparticle state to an incoherent state with temperature. Despite the metallic temperature dependence of resistivity, a well-defined Drude peak at low temperatures turns into a far-infrared peak with temperature. The peak energy shifts to higher frequencies and, simultaneously, the spectral weight is transferred to high frequencies beyond the electron band width. These characteristics imply that theta-(BEDT-TTF)2I3, so far believed to be a typical metal, is in fact a strongly correlated electron system with "bad-metal" character.

The magnetic state in LaCoO3 changes from the low spin state (S=0) to the mixed state with a thermally excited intermediate spin state (IS) (S=1) above about 50 K. The partially filled e(g) orbital in the IS state has a nature of Jahn-Teller (JT) distortion. The cooperative JT distortion causes an orbital order. We found that all Raman active phonon modes are affected by the excitation of IS Co3+ ions. Especially, the JT vibration mode shows anomalous temperature dependence.