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Cyprus experiences the highest level of water stress among European Union countries due to several interplaying factors such as rainfall variability and increasing water demand. These instigate the nation to build dams on almost all rivers of the island to satisfy the requirements for drinking water and irrigation. Many studies have been primarily conducted on assessing water availability for various uses, particularly for drinking water supply and irrigation. However, there is still a gap/less explored area in terms of a better understanding of changes in surface water over time. Thus, this study aims to evaluate the water surface area variation in Cyprus over the past four decades based on remote sensing products, timeseries analysis and trend detection. The result reveals a statistically significant increasing trend (p < 0.05) in water surface area between 1984–2021. However, following the completion of the final reservoir in 2010, a statistically significant decreasing trend (p < 0.05) was observed in the permanent water surface area. This decline is related to both climatic variability and increased water demands. We observed cycles of 6, 8, and 11 years in permanent water. These cycles indicate a recurring pattern of water scarcity, with severe implication already observed on both economic activity and agriculture. The recent decade has witnessed a decline in rainfall, and this is evident through the decrease in vegetation greenness in rainfed agricultural regions, highlighting its impact. Therefore, the findings of this study underscore not only the necessity for the development of infrastructure aimed at conserving water, but also reinforces the need to discuss water use priorities in Cyprus.

Introduction Deformational plagiocephaly (DP) is one of the most common cranial shape disorders in infancy. It is characterised by unilateral flattening of the skull due to head preference to one side. The literature suggests that DP is associated with comorbidities such as developmental delay, but the nature and prevalence of the comorbid impairments are still unclear and controversial. Therefore, our scoping review (ScR) aims to explore systematically the extent and nature of literature by identifying, mapping and categorising the most relevant comorbidities of DP in children up to the age of 2 years.Methods and analysis This protocol is based on the framework outlined by Arksey and O’Malley. A systematic search will be conducted to identify relevant full text studies from 1992 to 2021 using the databases of Cochrane, MEDLINE, Google Scholar, EMBASE, PubMed and University of Nicosia EBSCO. Two independent reviewers will screen abstracts and full articles in parallel, using specific inclusion and exclusion criteria. Specifically, this review will consider studies investigating DP and relevant comorbidities in children up to the age of 2 years of life without craniosynostosis, torticollis and any other diagnosed neurodevelopmental deficiency.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for ScR Checklist will be considered for results’ analysis and reporting. The results will be described in a narrative form in relation to the research question and in the context of the overall study purpose.Ethics and dissemination Research ethics approval is not required for this ScR since data will be retrieved from publicly available studies. Dissemination activities will include research findings’ submission for publication in a relevant peer-reviewed journal and presentation of the results at relevant conferences.Registration Our protocol was registered prospectively with the Open Science Framework (https://osf.io/48am3/).

Background: High-sensitivity cardiac troponin T (hs-cTnT) was proposed as a simple and useful diagnostic tool for cardiac amyloidosis (CA). We performed exploratory systemic screening using hs-cTnT to detect wild-type transthyretin CA (ATTRwt-CA) in outpatient and community-based settings., Methods and Results: This study was a prospective multicenter study including 8 internal medicine clinics in Kochi Prefecture, Japan. Consecutive individuals aged ≥70 years who visited those clinics as outpatients were enrolled. Patients with a prior diagnosis of CA or a history of heart failure hospitalization were excluded. We measured hs-cTnT levels in the enrolled individuals at each clinic, and those with elevated hs-cTnT levels (≥0.03ng/mL) received further detailed examination, including remeasurement of hs-cTnT. The diagnosis of ATTRwt-CA was confirmed by biopsy-proven transthyretin. Of 1,141 individuals enrolled in the study, 55 (4.8%) had elevated hs-cTnT levels. Of the 33 patients who underwent further examination, 22 had elevated hs-cTnT levels at remeasurement. Finally, 2 men were diagnosed with ATTRwt-CA. The prevalence of ATTRwt-CA was 9.1% (2/22) among patients with elevated hs-cTnT levels at two examinations, and at least 0.18% (2/1,141) in the whole study population., Conclusions: Measurement of hs-cTnT will help to screen for patients with undiagnosed ATTRwt-CA in primary care practice.

A 54-year-old man presented with a significant fourth heart sound (S4) and increased intensity of the second heart sound (S2), despite the absence of heart failure symptoms, in the second week of March 2024. Visualized phonocardiograms confirmed these findings, and further interviews revealed that he had suffered lifestyle changes, such as long commutes and sodium overload, while contributing to the response efforts in the 2024 Noto Peninsula Earthquake. Visualized phonocardiograms were also influential in determining the treatment strategy, persuading the patient to undergo a specific therapy, evaluating the therapeutic effects, and suggesting a new model for clinical practice.

The chemiluminescence (CL) feature and reactivity of the aromatic endoperoxide 9-phenyl-10-(2-phenylethynyl)anthracene endoperoxide (PPEA-O 2 ) were investigated in the crystalline state. For this, PPEA-O 2 crystals were prepared using dichloromethane and n -hexane. These crystals exhibited an α-phase structure containing n -hexane as a crystal solvent. The crystal structure of nonperoxidic anthracene (i.e., PPEA) was also confirmed. After optimizing heating conditions to 120 °C for the thermolytic reaction of PPEA-O 2 in crystals while maintaining the solid state, its CL characteristic and reactivity were investigated. Two key findings were derived: (1) dual-mode emission with maxima at 510 and 1275 nm and (2) distinct observation of CL emission at the first 2-3 min after the start of heating owing to the rapid thermolytic reaction coupled with n -hexane desorption. The 510 and 1275 nm emissions were attributed to the PPEA excimer and 1 O 2 ( 1 Δ g ), respectively. We proposed a mechanism involving the triplet-triplet annihilation of the excited triplet states of PPEA to explain excimer production with postulated pathways for generating these triplet states from PPEA-O 2 . The rapid thermolytic reaction of PPEA-O 2 in α-phase crystals with simultaneous n -hexane desorption was attributed to the formation of transient vacant spaces, which increased the molecular freedom necessary for the reaction ("transient vacant space effect"). Thus, the CL of PPEA-O 2 proved useful for identifying characteristic reactivity and analyzing the luminescence mechanism of aromatic endoperoxides in the crystalline state.

Aims: A fourth heart sound (S4) was reported to be almost never present in patients with amyloid light-chain cardiomyopathy. There have been no reports on S4 in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). This study aimed to clarify the clinical implications of S4 in patients with ATTRwt-CM., Methods and Results: Seventy-six patients with ATTRwt-CM (mean age: 80.4 ± 5.4 years, 68 males) who had undergone phonocardiography (PCG) were retrospectively assessed. We measured S4 amplitude on digitally recorded PCG. S4 was considered to be present when its amplitude was 1.0 mm or greater on the PCG. Distinct S4 was defined as S4 with an amplitude of 2.0 mm or greater, which is usually recognizable by auscultation. According to the rhythm and presence or absence of S4, the patients were divided into three groups, namely, sinus rhythm (SR) with S4, SR without S4, and non-SR. Non-SR consisted of atrial fibrillation, atrial flutter, and atrial tachycardia. Thirty-six patients were in SR and the remaining 40 patients were in non-SR. In the 36 patients in SR, S4 was shown by PCG to be present in 17 patients (47%), and distinct S4 was recognized in 7 patients (19%) by auscultation. In patients who were in SR, those with S4 had higher systolic blood pressure (124 ± 15 vs. 99 ± 8 mmHg, P < 0.001), lower level of plasma B-type natriuretic peptide (308 [interquartile range (IQR): 165, 354] vs. 508 [389, 765] pg/mL, P = 0.034) and lower level of high-sensitivity cardiac troponin T (0.068 [0.046, 0.089] vs. 0.109 [0.063, 0.148] ng/mL, P = 0.042) than those without S4. There was no significant difference in left atrium (LA) volume index or LA reservoir strain between patients with S4 and without S4. Patients with S4 had more preserved LA systolic function than those without S4 (peak atrial filling velocity: 53 ± 25 vs. 34 ± 9 cm/s, P = 0.033; LA contractile strain: 4.1 ± 2.1 vs. 1.6 ± 2.0%, P = 0.012). Patients in SR without S4 had worse short-term prognosis compared with the other two groups (generalized Wilcoxon test, P = 0.033)., Conclusions: S4 was present in 47% of the patients in SR with ATTRwt-CM. Patients in SR without S4 had more impaired LA systolic function than those in SR with S4. The absence of S4 portends a poor short-term prognosis in patients with ATTRwt-CM., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Surgeons' adaptability to robotic manipulation remains underexplored. This study evaluated the participants' first-touch robotic training skills using the hinotori surgical robot system and its simulator (hi-Sim) to assess adaptability., Methods: We enrolled 11 robotic surgeons (RS), 13 laparoscopic surgeons (LS), and 15 novices (N). After tutorial and training, participants performed pegboard tasks, camera and clutch operations, energizing operations, and suture sponge tasks on hi-Sim. They also completed a suture ligation task using the hinotori surgical robot system on a suture simulator. Median scores and task completion times were compared., Results: Pegboard task scores were 95.0%, 92.0%, and 91.5% for the RS, LS, and N groups, respectively, with differences between the RS group and LS and N groups. Camera and clutch operation scores were 93.1%, 49.7%, and 89.1%, respectively, showing differences between the RS group and LS and N groups. Energizing operation scores were 90.9%, 85.2%, and 95.0%, respectively, with a significant difference between the LS and N groups. Suture sponge task scores were 90.6%, 43.1%, and 46.2%, respectively, with differences between the RS group and LS and N groups. For the suture ligation task, completion times were 368 s, 666 s, and 1095 s, respectively, indicating differences among groups. Suture scores were 12, 10, and 7 points, respectively, with differences between the RS and N groups., Conclusion: First-touch simulator-based robotic skills were partially influenced by prior robotic surgical experience, while suturing skills were affected by overall surgical experience. Thus, robotic training programs should be tailored to individual adaptability., (© 2024. The Author(s).)

Background: Echocardiography remains the reference-standard imaging technique for assessing valvular heart disease (VHD), but artifacts like the 'color Doppler stripe' can complicate diagnosis. This artifact is not widely recognized and can mimic severe VHD, leading to potential misdiagnoses. We present two cases where color Doppler stripes mimicked severe VHD, highlighting the need for awareness and accurate interpretation in echocardiographic assessments., Case Presentations: Case 1: An 85-year-old patient was referred for mitral valve surgery due to suspected severe mitral regurgitation (MR). Upon evaluation, transthoracic echocardiography (TTE) showed mitral valve prolapse (P3) and a high-echoic, vibrating structure attached to the mitral valve, indicative of chordal rupture. Color Doppler echocardiography revealed strong systolic signals in the left atrium, mimicking severe MR. Transesophageal echocardiography (TEE) also detected the vibrating structure and color Doppler stripes in the left atrium, left ventricle, and outside the cardiac chambers. The PISA method on TEE indicated moderate MR and left ventriculography showed Sellers grade II MR. The artifact was identified as color Doppler stripes caused by the vibrating high-echoic structure from the ruptured chorda. Case 2: A 64-year-old patient with severe aortic stenosis, end-stage kidney disease requiring hemodialysis, and a history of coronary bypass grafting presented for routine follow-up. B-mode echocardiography showed a severely calcified tricuspid aortic valve with a vibrating calcified nodule and restricted opening, corresponding to severe aortic stenosis. During systole, color Doppler signals were observed around the aortic, pulmonary, and tricuspid valves, mimicking significant pulmonary stenosis and tricuspid regurgitation. However, pulmonary stenosis was ruled out as the pulmonary valve opening was normal. Mild tricuspid regurgitation was confirmed in the apical view., Conclusions: These cases highlight the diagnostic challenges posed by color Doppler stripes. Recognizing and understanding this artifact are crucial for the accurate diagnosis and management of VHD, ensuring appropriate treatment and patient outcomes., (© 2024. The Author(s).)

Objective: The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population., Participants: Ninety-eight young, healthy, underweight women participated in this study., Design: To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively., Results: Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR., Conclusions: Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels., 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 © 2024 Sato, Tamura, Kaga, Yamasaki, Kadowaki, Sugimoto, Nakagata, Someya, Nishida, Kawamori and Watada.)

Divergent total syntheses of binding pocket and peripherally modified tetrachlorovancomycins, a non-native synthetic glycopeptide, and their evaluation are disclosed. Central to the approach is the synthesis of a single late-stage intermediate that bears a residue 4 thioamide ([Ψ[C(═S)NH]Tpg 4 ]tetrachlorovancomycin ( 3 ), LLS 15 steps, 14% overall) as a precursor to either of two key pocket modifications and their pairing with any combination of two peripheral modifications conducted without protecting groups. A stereochemical simplification achieved by the addition of two aryl chlorides removes two synthetically challenging atropisomer centers in native glycopeptides and streamlines the synthesis. Key features include in a convergent epimerization-free thioacylation of the AB ring system amine with an N -thioacylbenzotriazolyl DE tetrapeptide (85%) followed by simultaneous room-temperature S N Ar macrocyclizations of the CD and DE ring systems (96%). The approach provided 3 from which [Ψ[C(═N)NH]Tpg 4 ]tetrachlorovancomycin ( 4 ) and [Ψ(CH 2 NH)Tpg 4 ]tetrachlorovancomycin ( 5 ) were prepared in a single-step and bear binding pocket modifications that convey dual d-Ala-d-Ala/d-Lac ligand binding to overcome vancomycin resistance. The newest maxamycin members are disclosed, bearing two additional peripheral modifications that introduce two independent synergistic MOAs that do not rely on native ligand binding for activity. Ligand binding properties of pocket-modified tetrachlorovancomycins 3 - 5 , antibacterial activity of a key compound series, and PK assessments of two tetrachloromaxamycins are reported.

Background: Cerebral small-vessel disease (cSVD), a key risk factor for stroke and dementia, has been linked to obesity and low bone mineral density (BMD). While obesity and low BMD are often inversely related, their coexistence may increase cSVD risk. We aimed to assess the prevalence of obesity and low BMD coexistence and its association with increased cSVD prevalence., Methods: This cross-sectional study used baseline data from the Bunkyo Health Study, which included 1531 community-dwelling adults aged 65-84 years without prior stroke history. All participants underwent dual-energy X-ray absorptiometry and brain magnetic resonance imaging. We defined cSVD as the presence of cerebral lacunar infarcts, cerebral microbleeds, periventricular hyperintensity or deep white matter hyperintensity. Obesity was defined by body mass index. Low BMD was defined as osteoporosis in women and osteopenia/osteoporosis in men. Participants were stratified by sex and classified based on obesity and low BMD presence or absence., Results: The prevalence of obesity with low BMD was 8.0 % in women and 7.8 % in men. The overall prevalence of cSVD was 23.2 %. Logistic regression analysis revealed that compared to the non-obese and non-low BMD group, the ORs [95 % CIs] for cSVD in the low BMD group, obesity group, and obesity with low BMD group were 1.55 [1.01-2.38], 1.24 [0.66-2.32], and 2.33 [1.20-4.50] in women, and 0.96 [0.60-1.54], 1.13 [0.65-1.96], and 2.80 [1.38-5.69] in men, respectively., Conclusion: The coexistence of obesity and low BMD, observed in approximately 8 % of older adults, was independently associated with the presence of cSVD., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Purpose: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear., Methods: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023., Results: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences., Conclusion: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss., The Trial Registration Number: B230165 (approved at December 26, 2023)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The genome is constantly exposed to DNA damage from endogenous and exogenous sources. Fine modulation of DNA repair, chromatin remodeling, and transcription factors is necessary for protecting genome integrity, but the precise mechanisms are still largely unclear. We found that after ionizing radiation (IR), global trimethylation of histone H3 at lysine 4 (H3K4me3) was decreased at an early (5 min) post-IR phase but increased at an intermediate (180 min) post-IR phase in both human and mouse hematopoietic cells. We demonstrated that PTIP, a component of the MLL histone methyltransferase complex, is required for H3K4me3 upregulation in the intermediate post-IR phase and promotes cell cycle arrest by epigenetically inducing a cell cycle inhibitor, PRDM1. In addition, we found that PTIP expression is specifically downregulated in acute myeloid leukemia patients. These findings collectively suggest that the PTIP-PRDM1 axis plays an essential role in proper DNA damage response and its deregulation contributes to leukemogenesis., (© 2024. The Author(s).)

Background/aim: Neskeep ® , an absorbable polyglycolic acid spacer, has been developed as the optimal material for spacer placement surgery. However, preventing its severe adhesion is a crucial concern. Therefore, we aimed to identify an effective anti-adhesion agent for Neskeep ® using rat models., Materials and Methods: Animal experiments were performed using 60 rats, which underwent Neskeep ® placement on the abdominal wall. Three types of anti-adhesion agents were employed, establishing four subgroups: Seprafilm ® , INTERCEED ® , AdSpray ® , and only Neskeep ® (control) groups. Rats were sacrificed on postoperative days 7, 14, and 28 to assess adhesion levels around the Neskeep ® Macroscopic visual assessment with the Lauder score and histopathological evaluation were performed to assess the degree of adhesion., Results: There were no significant differences in the proportion of Lauder scores on days 7 and 14 between the four groups. Histological evaluation revealed no significant differences between groups at any observation time. However, the mean Lauder scores at day 28 were 5.0, 1.6, 4.0, and 4.8 in the Neskeep ® , Seprafilm ® , INTERCEED ® , and AdSpray ® groups, respectively. The proportion of milder Lauder score was significantly higher in the Seprafilm ® group on day 28., Conclusion: Seprafilm ® may exhibit an anti-adhesive effect when used with Neskeep ® ., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The expression of nicotinic acetylcholine receptor (nAChR) subunits on various immune cells suggests their involvement in allergic rhinitis. However, how exactly they contribute to this pathogenesis is not yet confirmed. Our present study examined the therapeutic potential of GTS-21, an α7 nAChR agonist, for treating allergic rhinitis by employing its mouse models. GTS-21 treatment reduced allergen-induced immediate nasal response in ovalbumin (OVA)-sensitized model. However, nasal hyperresponsiveness or eosinophil infiltration elicited in either the OVA-sensitized or T helper 2 cell-transplanted model was not affected by GTS-21. GTS-21 did not alter allergen-induced passive cutaneous anaphylaxis response in anti-dinitrophenyl IgE-sensitized mice. This evidence implies GTS-21's potential to alleviate allergic rhinitis without perturbing T cells or mast cells.

Background: The relationships between electrocardiography (ECG) findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy (HCM) are not fully understood., Methods: One hundred forty patients (mean age: 62.9 ± 15.3 years, 96 men) with HCM were studied. We assessed the associations between ECG findings and echocardiographic findings including maximum left ventricular wall thickness, HCM subtypes and distribution of left ventricular hypertrophy (LVH): the LV was divided into basal, mid, and apical segments by dividing it into thirds along the long axis., Results: In ECG, LVH by voltage criteria, abnormal Q wave, negative T wave, and giant negative T wave (GNT) were observed in 74 (53 %), 30 (21 %), 132 (94 %), and 25 (18 %) of the patients, respectively. In two groups with and without an LVH pattern according to voltage criteria in ECG, there were no significant differences in maximum LV wall thickness, subtype of HCM, and distribution of LVH. Regarding an abnormal Q wave, the proportion of patients with LVH in the basal segment was significantly higher in patients with an abnormal Q wave than in patients without an abnormal Q wave (87 % vs 61 %, p = 0.008). An abnormal Q wave was not observed in patients with LVH confined to the apex. Patients with a GNT included patients with LVH located at only the apex (apical HCM), LVH from the mid segment to apex, and LVH from the base to apex. No GNT was found in patients with hypertrophy located in the upper region from the base to mid segment of the LV., Conclusions: In patients with HCM, there was no significant correlation between the presence of LVH by voltage criteria in ECG and echocardiographic findings. An abnormal Q wave was associated with disproportionate hypertrophy of the basal wall and a GNT reflected the presence of LVH in the apical segment., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pulsed cathodic arc-plasma deposition was employed to create a few nanometre-thick Pt overlayer on a 50 μm-thick Fe-Cr-Al metal (SUS) foil, resulting in an effective NH 3 oxidation catalyst fabrication. This catalyst exhibited a turnover frequency (TOF) exceeding 100 times that of Pt nanoparticles. In this study, Pt overlayer catalysts with varying degrees of surface roughness were fabricated using different metal foil substrates: mirror-polished (Pt/p-SUS), unpolished (Pt/SUS) and roughened by the formation of a surface oxide layer (Pt/Al 2 O 3 /SUS). The nanoscale roughness was comprehensively analysed using electron microscopy, laser scanning confocal microscopy and chemisorption techniques. NH 3 oxidation activity, measured at 200 °C, followed an increasing trend in the order of Pt/Al 2 O 3 /SUS < Pt/SUS < Pt/p-SUS, despite a decrease in the apparent Pt surface area in the same order. Consequently, the calculated TOF was markedly higher for Pt/p-SUS (267 min -1 ) compared to Pt/SUS (107 min -1 ) and Pt/Al 2 O 3 /SUS (≤22 min -1 ). The smooth Pt overlayer surface also favoured N 2 yield over N 2 O at this temperature. This discovery enhances our fundamental understanding of high-TOF NH 3 oxidation over Pt overlayer catalysts, which holds significance for the advancement and industrial implementation of selective NH 3 oxidation processes.

Background: Joint bleeding can lead to synovitis and arthropathy in people with hemophilia, reducing quality of life. Although early diagnosis is associated with improved therapeutic outcomes, diagnostic ultrasonography requires specialist experience. Artificial intelligence (AI) algorithms may support ultrasonography diagnoses., Objectives: This study will research, develop, and evaluate the diagnostic precision of an AI algorithm for detecting the presence or absence of hemarthrosis and synovitis in people with hemophilia., Methods: Elbow, knee, and ankle ultrasound images were obtained from people with hemophilia from January 2010 to March 2022. The images were used to train and test the AI models to estimate the presence/absence of hemarthrosis and synovitis. The primary endpoint was the area under the curve for the diagnostic precision to diagnose hemarthrosis and synovitis. Other endpoints were the rate of accuracy, precision, sensitivity, and specificity., Results: Out of 5649 images collected, 3435 were used for analysis. The area under the curve for hemarthrosis detection for the elbow, knee, and ankle joints was ≥0.87 and for synovitis, it was ≥0.90. The accuracy and precision for hemarthrosis detection were ≥0.74 and ≥0.67, respectively, and those for synovitis were ≥0.83 and ≥0.74, respectively. Analysis across people with hemophilia aged 10 to 60 years showed consistent results., Conclusion: AI models have the potential to aid diagnosis and enable earlier therapeutic interventions, helping people with hemophilia achieve healthy and active lives. Although AI models show potential in diagnosis, evidence is unclear on required control for abnormal findings. Long-term observation is crucial for assessing impact on joint health., (© 2024 The Authors.)

People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4 + count, CD4 + /CD8 + ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4 + count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH.

Background: Quadricuspid aortic valve (QAV) is a rare congenital disease. The clinical characteristics of this disease remain unclear except for those in relatively young patients reported from tertiary referral hospitals. The aim of this study was to determine the clinical features of QAV in a regional population., Methods and Results: We retrospectively investigated 25 340 consecutive patients over middle age (median age, 73 (IQR 65-80) years; range, 45-102 years) who underwent transthoracic echocardiography (TTE) at our institute during the period from April 2008 to December 2023. Eight (0.032%) of the patients (median age, 65 years; range, 47-91 years) were diagnosed with QAV. Six patients suffered from aortic regurgitation (AR), and one patient had mild aortic stenosis at the time of QAV diagnosis. Two patients who had severe AR at referral underwent aortic valve surgery. The severity of AR in the other patients was moderate or less. During a median follow-up period of 27 months (range, 1-171 months), none of the patients other than above two patients had cardiac events. One patient died from a non-cardiac cause at 94 years of age., Conclusions: Patients diagnosed with QAV after middle age, who do not exhibit severe valve insufficiency at the time of diagnosis, may not experience worse clinical outcomes. However, further research is required for a better understanding of the long-term outcomes., (© 2024 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Context: Older adults with sarcopenic obesity are at high risk for type 2 diabetes mellitus (T2DM). However, few East Asians have sarcopenic obesity. Since many East Asians have insulin resistance (IR) without obesity, it is possible that older East Asians with sarcopenia and IR might be at high risk for T2DM. However, this relationship has not been studied., Methods: This cross-sectional study included 1629 older adults aged 65 to 84 years registered in the Bunkyo Health Study. All underwent a 75-g oral glucose tolerance test and handgrip strength measurement. Participants were classified into 4 groups by possible sarcopenia (handgrip strength <28 kg in men and <18 kg in women) and IR status (triglyceride glucose [TyG] index ≥8.79 for men and ≥8.62 for women [third quartile]). Modified Poisson regression was used to estimate relative risk (RR) and 95% CIs for T2DM with adjustment for confounding factors., Results: The mean age was 73.1 ± 5.4 years. T2DM was diagnosed in 212 (13.0%) participants. After adjusting for age, sex, body mass index, use of lipid-lowering medications, hypertension, and cardiovascular disease, possible sarcopenia and IR were associated with T2DM, with their coexistence showing a notably stronger association (control: RR, 1.00 [Reference]; possible sarcopenia: RR, 1.55 [95% CI, 1.04-2.30]; IR: RR, 2.69 [95% CI, 1.99-3.65]; and IR possible sarcopenia: RR, 4.76 [95% CI, 3.34-6.79])., Conclusion: Possible sarcopenia based on low handgrip strength and IR based on the TyG index are independently associated with T2DM in older Japanese individuals. Their coexistence shows a particularly strong association with T2DM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Vizantin, 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose, has been developed as a safe immunostimulator on the basis of a structure-activity relationship study with trehalose 6,6'-dicorynomycolate. Our recent study indicated that vizantin acts as an effective Toll-like receptor-4 (TLR4) partial agonist to reduce the lethality of an immune shock caused by lipopolysaccharide (LPS). However, because vizantin has low solubility in water, the aqueous solution used in in vivo assay systems settles out in tens of minutes. Here, vizantin was chemically modified in an attempt to facilitate the preparation of an aqueous solution of the drug. This paper describes the concise synthesis of a water-soluble vizantin analogue in which all the hydroxyl groups of the sugar unit were replaced by sulfates. The vizantin derivative displayed micelle-forming ability in water and potent TLR-4 partial agonist activity.

Context: Older adults have a high prevalence of new-onset diabetes, often attributed to age-related decreases in insulin sensitivity and secretion. It remains unclear whether both insulin sensitivity and secretion continue to deteriorate after age 65., Objective: To investigate the effects of aging on glucose metabolism after age 65 and to identify its determinants., Methods: This cross-sectional study involved 1438 Japanese older adults without diabetes. All participants underwent a 75-g oral glucose tolerance test (OGTT). Body composition and fat distribution were measured with dual-energy X-ray absorptiometry and magnetic resonance imaging. Participants were divided into 4 groups by age (65-69, 70-74, 75-79, and 80-84 years) to compare differences in metabolic parameters., Results: Mean age and body mass index were 73.0 ± 5.4 years and 22.7 ± 3.0 kg/m 2 . The prevalence of newly diagnosed diabetes increased with age. Fasting glucose, fasting insulin, the area under the curve (AUC)-insulin/AUC-glucose and insulinogenic index were comparable between groups. AUC-glucose and AUC-insulin during OGTT were significantly higher and Matsuda index and disposition index (Matsuda index · AUC-insulin/AUC-glucose) were significantly lower in the age 80-84 group than in the age 65-69 group. Age-related fat accumulation, particularly increased visceral fat area (VFA), and elevated free fatty acid (FFA) levels were observed. Multiple regression revealed strong correlations of both Matsuda index and disposition index with VFA and FFA., Conclusion: Glucose tolerance declined with age in Japanese older adults, possibly due to age-related insulin resistance and β-cell deterioration associated with fat accumulation and elevated FFA levels., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)