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Background: Cefmetazole (CMZ) is a carbapenem-sparing option in the treatment of extended-spectrum beta-lactamase (ESBL)-producing bacterial infection. In this pilot study, we aimed to compare the effects of antimicrobial treatment (meropenem [MP] and CMZ) with those of no antimicrobial treatment (control group) on the microbiome., Methods: The study was a multicenter, prospective, observational pilot study conducted from October 2020 to October 2022. Feces and saliva samples were collected for microbiome analyses at two time points (early-period: days 1-3; and late-period: days 4-30) for the antimicrobial treatment group, and at one time point for the control group., Results: Five feces (MP-F and CMZ-F) and five saliva (MP-S and CMZ-S) samples were included in the MP and the CMZ groups. Ten feces (C-F) and saliva (C-S) samples were included in the control group. Group α diversity was notably lower in the late-period MP-F group than the control group as determined with the Shannon richness index. β diversity analysis of the feces samples based on weighted and unweighted UniFrac distances revealed distinctions in both the late-period CMZ-F and MP-F groups compared with the control group. Weighted UniFrac analysis showed that only the early-period MP-F group differed from the control group. In the saliva samples, weighted and unweighted UniFrac analyses showed significant differences between the control group and the early CMZ, late CMZ, and late MP groups., Conclusions: MP treatment may cause larger impact on the feces microbiome than CMZ in Japanese patients., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Prcis: Analysis of Ambient Interactive Zippy Estimation of Sequential Testing (AIZE) Rapid test variability in patients with stable glaucoma showed that the 95% prediction interval of the mean deviation (MD) value, potentially an index for judging progression, was ±1.63 to ±1.78 dB in early-to-moderate-stage patients., Objective: To explore the 95% prediction interval of the MD value using the AIZE Rapid test strategy for glaucoma observation., Patients and Methods: This study included 72 patients with stable or suspected glaucoma who underwent the imo AIZE Rapid test 3 times or more within 2 years. Both eyes from each patient were classified as better or worse eyes. They were divided based on baseline MD values into the following 4 groups: MD > -3 dB, -6 dB < MD ≤ -3 dB, -12 dB < MD ≤ -6 dB, and MD ≤ -12 dB. The variability of MD during the observation period and the 95% prediction intervals were analyzed. Pointwise variability of limits at each test location was also calculated., Results: The numbers of better and worse eyes included in the study were 46 and 33. The median follow-up period was 1.3 years (range: 0.5 to 1.9 y). The 95% prediction intervals for MD values were ±1.41 dB for better eyes (n = 46) and ±1.47 dB for worse eyes (n = 33). The 95% prediction intervals in the MD > -3 dB, -6 dB < MD ≤ -3 dB, -12 dB < MD ≤ -6 dB, and MD ≤ -12 dB groups were ±1.63 dB, ±1.34 dB, ±1.78 dB, and ±1.33 dB, respectively. Pointwise variability of worse eyes was larger than that of better eyes, especially between 10 to 15 dB., Conclusion: In the case of a difference in MD greater than the 95% prediction intervals when compared with the previous visual field result, we should pay much attention to the possibility of progression of the glaucomatous visual field in patients with stable glaucoma., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies' production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment., Methods: Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1 month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment., Results: Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6-10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment., Conclusions: In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity., (© 2024. The Author(s).)

Aims/introduction: We previously showed that glucokinase haploinsufficiency improves the glucose tolerance of db/db mice by preserving pancreatic β-cell mass and function. In the present study, we aimed to determine the effects of glucokinase haploinsufficiency on the β-cell mass and function of long-term high-fat, high-sucrose (HFHS) diet-fed mice., Materials and Methods: Four-week-old male glucokinase haploinsufficient (Gck +/- ) mice and 4-week-old male wild-type (Gck +/+ ) mice (controls) were each divided into two groups: an HFHS diet-fed group and a normal chow-fed group, and the four groups were followed until 16, 40 or 60 weeks-of-age. Their glucose tolerance, glucose-stimulated insulin secretion and β-cell mass were evaluated. In addition, islets were isolated from 40-week-old mice, and the expression of key genes was compared., Results: Gck +/- HFHS mice had smaller compensatory increases in β-cell mass and glucose-stimulated insulin secretion than Gck +/+ HFHS mice, and their glucose tolerance deteriorated from 16 to 40 weeks-of-age. However, their β-cell mass and glucose-stimulated insulin secretion did not decrease between 40 and 60 weeks-of-age, but rather, tended to increase, and there was no progressive deterioration in glucose tolerance. The expression of Aldh1a3 in pancreatic islets, which is high in several models of diabetes and is associated with an impairment in β-cell function, was high in Gck +/+ HFHS mice, but not in Gck +/- HFHS mice., Conclusions: Glucokinase haploinsufficiency prevents the progressive deterioration of pancreatic β-cell mass/function and glucose tolerance in long-term HFHS diet-fed mice., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

International travel is a risk factor for acquiring sexually transmitted infections (STIs) owing to factors such as increased sexual opportunities, a sense of freedom, and the allure of the sex industry. We investigated the incidence of travel-associated STIs in Japan using data from the Japan Registry for Infectious Diseases from Abroad (J-RIDA) reported by 17 participating medical institutions between October 2017 and December 2022. Data were collected on the patients' age, sex, nationality, chief complaint, whether they had visited a travel clinic before travel, travel history, and final diagnosis. Of 4545 cases of travel-associated illness reported, 52 (1.1%) were STIs. Most patients with STIs were male (81%) with a median age of 31 years. HIV (17%), genital herpes (13%), syphilis (13%), and gonorrhea (12%) were the most frequently reported STIs. Only one patient had visited a travel clinic before travel. Promoting awareness and vaccination is crucial for preventing travel-associated STIs., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Background: Streptococcal toxic shock syndrome (STSS) is a life-threatening condition caused by beta-hemolytic streptococci (BHS). Streptococcus pyogenes is the main causative agent of this disease; other BHS such as Streptococcus agalactiae or Streptococcus dysgalactiae could also cause STSS. However, the clinical characteristics of STSS caused by other types of BHS remain poorly understood. In this study, we evaluated the likelihood of STSS development in various streptococcal species., Methods: We conducted a retrospective observational study using adult medical records of patients with invasive BHS in a tertiary care institution from 2002 to 2022 and classified them into STSS or non-STSS groups. Multivariable analysis of bacterial species adjusted for age and diabetes mellitus was conducted. S pyogenes cases were propensity-matched (1:4) to non-pyogenes BHS cases., Results: A total of 43 STSS and 285 non-STSS cases were identified. S pyogenes , S agalactiae , and S dysgalactiae accounted for 17, 13, and 13 STSS cases, respectively. The crude mortality of STSS was approximately 35% in all groups. A multivariable analysis suggested that STSS was less frequent in S agalactiae and S dysgalactiae cases with odds ratio 0.24 (95% confidence interval [CI], 0.10-0.54; P < .001) and 0.23 (95% CI, .10-.55; P < .001), respectively. Propensity score matching showed that S pyogenes caused STSS more frequently than other BHS cases with an odds ratio of 3.28 (95% CI 1.21-8.77; P = .010)., Conclusions: This study described and compared the clinical characteristics of STSS caused by different BHS. We demonstrated that S pyogenes caused STSS more often than other BHS., Competing Interests: Potential Conflicts of Interest. The authors declare that there is no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with β-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). β-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group ( P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = -0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in β-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Improvements in BUN after transplantation were associated with improvements in β-cell function. NEW & NOTEWORTHY In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in β-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus.

Trypanosoma brucei brucei is a parasitic protist that expresses cell surface proteins modified with complex-type N-linked glycan (NLG), like multicellular organisms. However, little is known about the role of complex-type NLG. In T. b. brucei, it has been shown that either one of the glycosyltransferases, TbGT11 or TbGT15, is sufficient to initiate the synthesis of complex-type NLG. To clarify the role of complex-type NLG, it is necessary to generate cells lacking both enzymes. Therefore, we deleted TbGT11 and TbGT15 from the genome of T. b. brucei for the phenotypic examination. The mutant strain grew in culture, with reduced maximum cell density; showed decreased susceptibility to normal human serum, which contains trypanolytic factors; and lacked uptake of the haptoglobin-hemoglobin complex. These data indicate that protein modification by complex-type NLG is not essential but is required for receptor function., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The management of persistent symptomatic coronavirus disease 2019 (COVID-19) infections in immunocompromised patients remains unclear. Here, we present the first case of successful antiviral therapy (nirmatrelvir/ritonavir and remdesivir) in combination with intravenous immunoglobulin (IVIg) in a patient who had received CD20 depleting therapy for follicular lymphoma and experienced recurrent COVID-19 relapses. After the patient received IVIg treatment, the viral load decreased without recurrence. Subsequently, it was found that the anti-spike antibody titer in the administered immunoglobulin was high at 9528.0 binding antibody units/mL. Our case highlights the potential of combination therapy with selective IVIg and antiviral drugs for relapsed immunocompromised COVID-19 patients who have received CD20 depleting therapy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Oral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world., Methods: We retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65-74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity., Results: We studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (- 13.1 ± 7.5 mmol/mol and - 3.0 ± 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = -0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = -0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4)., Conclusions: Oral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of ≥ 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence., (© 2024. The Author(s).)

Asynchronous migration of insect herbivores and their host plants towards higher elevations following climate warming is expected to generate novel plant-insect interactions. While the disassociation of specialised interactions can challenge species' persistence, consequences for specialised low-elevation insect herbivores encountering novel high-elevation plants under climate change remain largely unknown. To explore the ability of two low-elevation Lepidoptera species, Melitaea celadussa and Zygaena filipendulae , to undergo shifts from low- to high-elevation host plants, we combined a translocation experiment performed at two elevations in the Swiss Alps with experiments conducted under controlled conditions. Specifically, we exposed M . celadussa and Z . filipendulae to current low- and congeneric high-elevation host plants, to test how shifts in host plant use impact oviposition probability, number of eggs clutches laid, caterpillar feeding preference and growth, pupation rate and wing size. While our study shows that both M . celadussa and Z . filipendulae can oviposit and feed on novel high-elevation host plants, we reveal strong preferences towards ovipositing and feeding on current low-elevation host plants. In addition, shifts from current low- to novel high-elevation host plants reduced pupation rates as well as wing size for M . celadussa , while caterpillar growth was unaffected by host plant identity for both species. Our study suggests that populations of M . celadussa and Z . filipendulae have the ability to undergo host plant shifts under climate change. However, these shifts may impact the ability of populations to respond to rapid climate change by altering developmental processes and morphology. Our study highlights the importance of considering altered biotic interactions when predicting consequences for natural populations facing novel abiotic and biotic environments., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions., Competing Interests: Satoshi Shinozaki, Hiroyuki Osawa, and Yoshimasa Miura have received honoraria from Takeda and Otsuka Pharmaceuticals. Hirotsugu Sakamoto, Tomonori Yano, and Hironori Yamamoto have received honoraria from Takeda Pharmaceutical. All other authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 ± 12.6 years; body mass index 29.6 ± 6.0 kg/m 2 ) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 ± 1.11% to 6.88 ± 0.91% (p < 0.001) and 80.2 ± 19.2 kg to 77.6 ± 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting.

Context: Whether continuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) or switching to oral semaglutide is more beneficial for β-cell function is unclear., Objective: To assess the efficacy of switching from DPP-4is to oral semaglutide for β-cell function compared with DPP-4i continuation., Methods: Post hoc analysis of SWITCH-SEMA 2, a multicenter prospective randomized controlled trial on the switch to oral semaglutide vs DPP-4i continuation without dose adjustment for 24 weeks in subjects with type 2 diabetes treated with DPP-4is, was conducted. Changes in markers for glucose metabolism, including homeostatic model assessment (HOMA2) scores and disposition index (DI), were compared between the groups., Results: A total of 146 subjects (semaglutide group, 69; DPP-4i group, 77) were analyzed. In the semaglutide group, glycemic control, liver enzyme deviations, and lipid profiles improved after 24 weeks. Regarding indices for β-cell function, changes in HOMA2-β as well as DI, reflecting the ability of β-cells to compensate for insulin resistance, were significantly higher in the semaglutide group compared with the DPP-4i group (mean change, +10.4 vs +0.6 in HOMA2-β [P = .001] and +0.09 vs 0.0 in DI [P < .001]). Improvement in DI in the semaglutide group was correlated significantly to changes in body mass index (BMI), HbA1c, and fatty liver index reflecting liver steatosis. Multiple linear regression analysis revealed that dose of semaglutide (≥ 7 mg/day), reduction in fatty liver index, and metformin nonuse were independently associated with improvement of DI., Conclusion: Switching to oral semaglutide ameliorated β-cell function compared with DPP-4is, presumably via tissue-to-tissue crosstalk between liver and β-cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Backgruound: Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting., Methods: We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status., Results: Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05)., Conclusion: A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.

The proinsulin-to-C-peptide (PI:C) ratio is an index applied during the early stage of pancreatic β-cell dysfunction. The aim of this study was to identify the characteristics associated with the PI:C ratio to discuss pancreatic β-cell dysfunction progression during the natural course of type 2 diabetes and its relationship with glycemic management. This multicenter, prospective observational study included 272 outpatients with type 2 diabetes. Continuous glucose monitoring was performed and fasting blood samples were collected and analyzed. We identified the clinical factors associated with the PI:C ratio by multiple regression analysis. The mean age of the cohort was 68.0 years, mean hemoglobin A1c 7.1% (54 mmol/mol), and mean body mass index 24.9 kg/m 2 . Multiple regression analysis showed that a prolonged time above the target glucose range (>180 mg/dL) and high body mass index contributed to a high PI:C ratio. However, no associations were found between the PI:C ratio and glucose variability indices. These findings suggested that the PI:C ratio is positively associated with a prolonged hyperglycemic time in type 2 diabetes, whereas its relationship with glucose variability remains unclear.

Aims: This study aimed to clarify the real-world status of lipid management in outpatients with type 2 diabetes (T2DM) following the 2022 revision of the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. It also aimed to evaluate characteristics associated with the failure to achieve management targets., Materials and Methods: In this post-hoc analysis of a multicenter, cross-sectional study, we included Japanese outpatients with T2DM undergoing primary prevention of atherosclerotic cardiovascular diseases (ASCVD) who provided fasting blood samples. The frequency and determinants of achieving low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) targets were assessed., Results: Among 223 participants with a mean age of 67 and mean HbA1c of 7.1%, 61 had no history of peripheral arterial disease, microvascular complications, or smoking. Out of the 223 participants, 64.1% (95% CI: 57.6-70.1%) achieved the LDL-C target. In multivariate logistic regression analysis, being female (odds ratio [OR] 3.139, P = 0.0011), having diabetic nephropathy (OR 2.868, P = 0.0021), smoking (OR 2.292, P = 0.0281), and non-use of statins (OR 4.857, P < 0.0001) were independently associated with non-achievement. For non-HDL-C, 65.6% (95% CI: 58.1%-70.6%) of patients met the target. Having diabetic neuropathy (OR 2.428, P = 0.0054), smoking (OR 2.008, P = 0.0478), and non-use of statins (OR 2.277, P = 0.0112) were identified as factors associated with non-achievement., Conclusions: Low achievement rate of revised lipid management targets for ASCVD primary prevention in T2DM was unveiled. Assessing comorbidities, encouraging smoking cessation, and prioritizing statin use are considered., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The biosynthesis of N-linked glycan precursors in the endoplasmic reticulum is important for many eukaryotes. In particular, the synthesis of Man 5 GlcNAc 2 -PP-dolichol (M5-DLO) at the cytoplasmic face of the endoplasmic reticulum is essential for maintaining cellular functions. In Trypanosoma brucei, the unicellular organism that causes African trypanosomiasis, homologs of the mannosyltransferases ALG2 and ALG11, which are involved in the biosynthesis of M5-DLO, are found, but the effects of their deletion on cells remain unknown. In this study, we generated conditional gene knockout strains of TbALG2 and TbALG11 in the bloodstream form T. brucei. Decreased N-linked glycosylation and cell death were observed in both strains under non-permissive conditions, with TbALG2 having a greater effect than TbALG11. Transcriptomic analysis of cells losing expression of TbALG11 showed decrease in mRNAs for enzymes involved in glucose metabolism and increase in mRNAs for procyclins and variant surface glycoproteins. These results indicate that the M5-DLO biosynthetic pathway is essential for the proliferation of the bloodstream form T. brucei. They also suggest that the failure of this pathway induces the transcriptomic change., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

ProNGF (nerve growth factor) is a precursor of NGF and a signaling peptide exerting opposite effects on neuronal cells, i.e., apoptotic or neuritogenic. The conflicting biological activity of proNGF depends on the relative levels of two membrane receptors, TrkA and p75NTR. The effect of proNGF depends on the expression levels of these receptor proteins and their affinity to proNGF. Since the affinity of proteins has been studied with various recombinant proteins, it is worth comparing the affinity of these proteins within one experiment with the same method. This study examined the affinity between a recombinant proNGF and p75NTR expressed in common systems: bacterial, insect, and mammalian cells. The extracellular domain of p75NTR expressed in the insect or mammalian systems bound to native mature NGF, with a higher affinity for the insect receptor. The uncleavable proNGF was expressed in the three systems and they showed neuritogenic activity in PC12 cells. These recombinant proteins were used to compare their binding affinity to p75NTR. The insect p75NTR showed a higher binding affinity to proNGF than the mammalian p75NTR. The insect p75NTR bound proNGF from the insect system with the highest affinity, then from the mammalian system, and the lowest from the bacterial system. Conversely, the mammalian p75NTR showed no such preference for proNGF. Because the recombinant proNGF and p75NTR from different expression systems are supposed to have the same amino acid sequences, these differences in the affinity depend likely on their post-translational modifications, most probably on their glycans. Each recombinant proNGF and p75NTR in various expression systems exhibited different mobilities on SDS-PAGE and reactivities with glycosidases and lectins., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aim: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) continuation, in people with type 2 diabetes., Materials and Methods: In this multicentre, open-label, prospective, randomized, parallel-group comparison study, participants receiving DPP-4is were either switched to oral semaglutide (3-14 mg/day) or continued on DPP-4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored., Results: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP-4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP-4i continuation [-0.65 (95% confidence interval: -0.79, -0.51) vs. +0.05 (95% confidence interval: -0.07, 0.16) (p < .001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP-4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2-R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms., Conclusions: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP-4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance., (© 2023 John Wiley & Sons Ltd.)

The post-hoc study, derived from our previous prospective observational study, investigated the association between fasting serum proinsulin levels and hepatic steatosis in people with type 2 diabetes. The severity of hepatic steatosis was assessed using the fatty liver index. A total of 268 participants were divided into three groups: low (n = 110), moderate (n = 75), and high fatty liver index (n = 83). In both the crude and age/sex-adjusted analysis, logarithm-transformed proinsulin was significantly higher in the high fatty liver index group than in the low or moderate groups (all p < 0.01). The moderate fatty liver index group showed higher logarithm-transformed proinsulin than the low group (both p < 0.01). Positive associations between proinsulin and fatty liver index shown in this study would support an involvement of hepato-pancreatic crosstalk in the pathophysiology of type 2 diabetes.

Background: To date, few studies from the Asian region have reported the effectiveness of messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccines against disease progression and death after hospitalization., Methods: We evaluated the data from the COVID-19 registry in Japan during the delta- and omicron-dominant phases. A propensity score-matched cohort study was conducted between the incompletely (0-1 dose) and fully (2 doses) vaccinated groups during the delta-dominant phase and among the incompletely, fully, and booster (3 doses) vaccinated groups during the omicron-dominant phase., Results: In the delta-dominant phase, 411 pairs were matched. The fully vaccinated group showed a significantly lower oxygen supplementation rate (24.1 % vs. 41.1 %, p < 0.001) but little difference in the mortality rate (2.2 % vs. 2.9 %, p = 0.66). In the omicron-dominant phase, 1494 pairs from the incompletely and fully vaccinated groups, and 425 pairs from the fully and booster vaccinated groups were matched. Full vaccination reduced both the oxygen supplementation rate (18.6 % vs 25.7 %, p < 0.001) and mortality rate (0.7 % vs 2.3 %, p < 0.001). Booster vaccination showed little difference in either the rate of oxygen supplementation (21.2 % vs. 24.7 %, p = 0.25) or mortality (1.2 % vs. 2.6 %, p = 0.21) compared with full vaccination., Conclusions: Full vaccination reduced disease severity during the delta- and omicron-dominant phases; booster vaccination did not further enhance the protective effects against disease progression during the omicron-dominant phase compared to full vaccination. Future vaccine strategies and policy decisions should consider preventing infection or disease progression in the target population, as well as the characteristics of the dominant variant in that phase., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: SS is an associate editor of the Western Pacific Surveillance and Response journal. She was not involved in the editorial decision to publish this article. The other authors have no conflicts of interest to declare.