Nagoya Kyouritsu Hospital

The need for SARS-CoV-2 vaccines with improved potency, lower reactogenicity, broader coverage, and prolonged protection persists. We examined the safety and immunogenicity of two ferritin scaffold-based self-assembling SARS-CoV-2 mRNA virus-like particle (VLP) vaccines. In this, randomized, Phase I, open-label, active-controlled study (www. govNCT06147063) participants received a single 5μg or 10μg intramuscular injection of AZD9838 (BA.4/5 variant) or AZD6563 (XBB.1.5 variant), or 30μg BNT162b2, a licensed mRNA vaccine (XBB.1.5 variant). The primary safety endpoint was the incidence of solicited adverse reactions (ARs) through Day 8, unsolicited adverse events (AEs) through Day 29, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) through Day 361. The primary immunogenicity endpoint was to characterize the neutralizing antibody (nAb) responses to the ancestral and Omicron (BA.4/5, XBB.1.5) variants at Day 29; characterization of nAb response to Omicron JN.1 was an exploratory analysis. In total, 166 participants aged 18-64years and 76 participants ≥65years of age were vaccinated. AZD9838 and AZD6563 were well-tolerated at both dosages. Overall, fewer solicited ARs were reported with AZD9838 and AZD6563 versus BNT162b2. Unsolicited AEs were similar between groups; no related SAEs, AESIs, or MAAEs were reported to Day 180. Day 29 nAb GMTs were higher following 10μg AZD6563 versus 5μg and higher than AZD9838 across variants and age groups, remaining above baseline and similar to BNT162b2 at Day 180; 10μg AZD6563 resulted in nAb GMTs similar to BNT162b2 in both age groups. By combining mRNA vaccine technology with VLP-based antigen display, we developed two candidate SARS-CoV-2 vaccines, AZD9838 and AZD6563, that were well tolerated versus a licensed mRNA vaccine, BNT162b2. Furthermore, the variant-matched AZD6563 generated a similar immunogenicity to BNT162b2 but at one third of the dosage (10μg versus 30μg).

ABSTRACT Aims Climatic factors, such as water stress, and chronic anthropogenic disturbances, such as biomass extraction, influence tropical forest community structure, richness and composition. However, while the individual effects of these two drivers on plant communities are well‐studied, their interactive effects are not. Location We conducted a study in the northern Western Ghats of Maharashtra, India. Moist tropical forests in India's Western Ghats face a dual threat from increasingly erratic precipitation (and consequent water stress) and an intensifying anthropogenic footprint. Methods We sampled 120 tree plots (0.05 ha each) across forests with varying histories of biomass extraction and a gradient of climate water deficit (a proxy for water stress) within a 15,000‐km 2 landscape. Using generalised linear and mixed‐effects models, we tested the influence of chronic disturbance and climate water deficit on overall tree species richness, evergreen and deciduous tree species richness and the proportion of evergreen trees. Results We recorded 7001 individual trees belonging to 192 species. Tree composition varied across disturbance and elevation categories. Overall and evergreen tree species richness were significantly lower, while deciduous tree species richness was higher in repeatedly disturbed forests compared to less disturbed sites. Deciduous tree species richness increased more steeply with increasing water stress in repeatedly disturbed sites. Meanwhile, evergreen species richness increased with decreasing water stress. Conclusions Overall, we show that chronic disturbance reduces evergreen tree species and favours more widely distributed deciduous species. In the northern Western Ghats, where much of the remaining forest cover is disturbed and dominated by deciduous tree species, the persistence of the evergreen tree flora hinges on protecting existing evergreen forest patches from disturbances and restoring secondary forests with appropriate evergreen tree species.

The phase III SELECT-MONOTHERAPY trial (NCT02706951) demonstrated the safety and efficacy of upadacitinib (UPA) monotherapy through 84 weeks in patients with rheumatoid arthritis who responded inadequately to methotrexate. Here we report week 260 results. Patients were randomised to continue methotrexate or UPA 15 mg (UPA15) or 30 mg (UPA30) monotherapy for 14 weeks. From week 14, patients continuing methotrexate switched to UPA15 or UPA30 per prespecified assignment; patients randomised to UPA continued treatment. Following a protocol amendment, all cohorts switched to open-label UPA15. Safety was summarised using exposure-adjusted event and incidence rates. Efficacy was reported as observed and using non-responder imputation (NRI). Of 648 randomised patients, 598 entered the long-term extension. Of these, 249 (41.6%) discontinued study drug by week 260 primarily due to adverse events (14.5%), consent withdrawal (9.9%), lost to follow-up (3.3%), lack of efficacy (2.2%), COVID-19 (0.7%) or other reasons (11.0%). Rates of herpes zoster, non-melanoma skin cancer, hepatic disorder, neutropenia, lymphopenia and creatine kinase elevation were higher with UPA30 versus UPA15. Long-term UPA safety data were consistent with the established UPA safety profile. Based on NRI, >39% of patients treated continuously with UPA achieved low disease activity per Clinical Disease Activity Index ≤10 (UPA15, n=93/217; UPA30, n=91/215) and 28-joint Disease Activity Score using C reactive protein ≤3.2 (UPA15, n=90/217; UPA30, n=94/215) at week 260. Efficacy was similar among patients switching from methotrexate to UPA. No new safety risks were identified with long-term UPA treatment. UPA monotherapy was efficacious in treating rheumatoid arthritis through week 260. NCT02706951.

IntroductionThe month of Ramadan, a sacred period in the Islamic calendar, is a time of fasting, prayer, and reflection for millions of Muslims worldwide. While the effects of fasting on physical and mental health have been extensively studied, there has been little focus on its specific impact on sexual life, particularly in the Tunisian context.ObjectivesThe aim of our research was to study the opinions of Tunisians regarding their sexual behavior during the month of Ramadan.MethodsThis was a retrospective, descriptive, and comparative study conducted through an online survey among Tunisian adults. Data collection was carried out via a self-administered online questionnaire during Ramadan 2024, from March 21 to April 4, 2024. Two reminders were sent and the anonymity of the responses was guaranteed.ResultsOur study included 130 Tunisian adults with a mean age of 28.69 years. The majority of our population resided in urban areas (98.5%), 43.8% were single where 29.2% were in a relationship and both genders were equally represented (53.1% female, 46.9% male). The majority of participants identified as heterosexual (89.2%). During Ramadan, 78.5% of participants fasted, and 77.7% believed sexual activity was permissible during this period. Overall, 44.6% of participants felt that fasting had a negative impact on sexual behavior, 30.7% on sexual desire, and 26% on sexual performance. More than 70% reported that fasting influenced their sexual behavior, primarily in a negative way (44.6%). Among those who perceived an impact (n=93), changes were mostly noted in the timing (77.7%) and frequency of sexual activities (75.5%). Furthermore, 72.3% of participants reported that fasting influenced their sexual desire, with 40.9% perceiving this influence positively. Behavioral factors were identified as the most common cause of these changes (52.1%), followed by religious reasons (27.7%) and societal factors (11.7%). Significant gender differences were observed, with women being more affected by religious factors (p=0.02), while men were more influenced by behavioral factors (p=0.03). Women also reported a significantly greater impact on the frequency of sexual activity compared to men (p=0.012) and perceived a more significant negative impact of fasting on sexual performance compared to men (p=0.06).ConclusionsOur study indicates that Ramadan fasting significantly affects the sexual lives of Tunisians, driven by sociocultural, religious, and physiological factors. This highlights the need for culturally sensitive sexual education and targeted health policies to ensure accessible and inclusive care during Ramadan.Disclosure of InterestNone Declared

Cervical spine injuries in the elderly (defined as individuals aged 65years and older) are increasing, often resulting from falls and minor trauma. Prognosis varies widely, influenced by multiple factors. This study aimed to develop a deep-learning-based predictive model for post-injury outcomes. This study analyzed a nationwide dataset from the Japan Association of Spine Surgeons with Ambition, comprising 1512 elderly patients (aged 65years and older) with cervical spine injuries from 2010 to 2020. Deep learning predictive models were constructed for residence, mobility, and the American Spinal Injury Association Impairment Scale (AIS). The model's performance was compared with that of a traditional statistical analysis. The deep-learning model predicted the residence and AIS outcomes with varying accuracies. The highest accuracy was observed in predicting residence one year post-injury. The model also identified that the AIS score at discharge was significantly predicted by upper extremity trauma, mobility, and elbow extension strength. The deep learning model highlighted factors, such as upper extremity trauma, that were not considered significant in the traditional statistical analysis. Our deep learning-based model offers a novel method for predicting outcomes following cervical spine injuries in the elderly population. The model is highly accurate and provides additional insights into potential prognostic factors. Such models can improve patient care and individualize future interventions.

ABSTRACTThe advance care directive is a device for deciding one’s own end-of-life care by giving directions on terminal care in advance. A family discussion in the field about these documents is essential to decide the best management measures.

This study presents a comparison of novel pregnant model phantoms with a handmade phantom in terms of shape and radiation measurement points to determine which model is more suitable for measuring the foetal radiation dose during x-ray examinations. Novel pregnant model phantoms were constructed using an anthropomorphic phantom in combination with two differently-sized custom-made abdomen phantoms simulating pregnancy, which were constructed from a polyurethane resin. The size and shape of the polyurethane resin were designed based on abdominal sizes and shapes collected from the computed tomography examinations at 18 pregnant patients of one hospital. The handmade pregnant model phantom was constructed using an anthropomorphic phantom and a beach ball containing water. Compared with the handmade phantom, there were additional dose measurement points on the novel pregnant model phantoms. Our model phantoms improved upon the handmade phantom in terms of shape and radiation measurement points. We produced pregnant model phantoms that simulated the shapes and sizes of actual patients for the first time.

PurposeEndovascular treatment of posterior communicating artery aneurysms with fetal-type posterior communicating artery originating from the aneurysm dome is often challenging because, with conventional techniques, dense packing of aneurysms for posterior communicating artery preservation is difficult; moreover, flow-diversion devices are reportedly less effective. Herein, we describe a novel method called the λ stenting technique that involves deploying stents into the internal carotid artery and posterior communicating artery.MethodsBetween January 2018 and September 2020, the λ stenting technique was performed to treat eight consecutive cases of aneurysms. All target aneurysms had a wide neck (dome/neck ratio < 2), a fetal-type posterior communicating artery with hypoplastic P1, and a posterior communicating artery originating from the aneurysm dome. The origin of the posterior communicating artery from the aneurysm, relative to the internal carotid artery, was steep (< 90°: V shape).ResultsThe maximum aneurysm size was 8.0 ± 1.9 mm (6–12 mm). The average packing density (excluding one regrowth case) was 32.7 ± 4.2% (26.8–39.1%). Initial occlusion was complete occlusion in 6 (75.0%) patients and neck remnants in 2 (25.0%) patients. Follow-up angiography was performed at 18.4 ± 11.6 months (3–38 months). There were no perioperative complications or reinterventions required during the study period.ConclusionThe λ stenting technique enabled dense coil packing and preservation of the posterior communicating artery. This technique enabled safe and stable coil embolization. Thus, it could become an alternative treatment option for this sub-type of intracranial aneurysms.

BackgroundA triple-coaxial (triaxial) system, which consists of a small microcatheter,a large microcatheter, and a 4-Fr. catheter, has been reported to allowsuper-selective catheterization. A 1.6-Fr. microcatheter has recently becomeavailable as the small microcatheter for the triaxial system, in addition to0.014-in. pushable bare platinum coils that may be introduced into the1.6-Fr. microcatheter.PurposeThe purpose of the present study was to evaluate the feasibility of 0.014-in.pushable bare platinum coils in embolization through the 1.6-Fr.microcatheter of the triaxial system.Material and MethodsBetween November 2015 and October 2019, 19 embolizations were performed on 18patients, 9 males and 9 females with a median age of 77 years (range, 41–88years), using 0.014-in. pushable bare platinum coils through the 1.6-Fr.microcatheter of the triaxial system. The technical success rate, clinicalsuccess rate, and complications associated with the procedure were assessed.Technical success was defined as the successful delivery and placement of0.014-in. pushable bare platinum coils, and clinical success as theimmediate postembolic complete cessation of blood flow confirmed by digitalsubtraction angiography.ResultsEighty-four 0.014-in. pushable bare platinum coils were delivered and 19arteries were successfully embolized. The median number of 0.014-in.pushable bare platinum coils was 4 (range, 1–12). The technical success ratewas 100% (84/84) and the clinical success rate was also 100% (19/19). Therewere no complications associated with the procedures.ConclusionThe use of 0.014-in. pushable bare platinum coils in super-selectiveembolization through the 1.6-Fr. microcatheter of the triaxial systemappears to be feasible and safe.