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In mammals, a pair of ejaculatory ducts exists in the urethra at the seminal colliculus. The detailed anatomical structures of the distal end of the ejaculatory ducts of Sprague-Dawley rats were investigated by the computer-assisted three-dimensional reconstruction analysis using light-microscopic serial sections. A three-dimensional reconstruction revealed that in adult rats, the ejaculatory sinus pair consists of two parts: the cranial section - a compartment region composed of a fusion of the ampullary gland duct and the seminal vesicle duct, and the caudal section - a grooved region composed of a long slitlike ejaculatory ostium that extends into the urethra on both sides of the seminal colliculus. But the sphincter structure was not observed. The long axis of the compartment region was approximately 58 lm in length, and that of the groove region was approximately 495 μm. Although many epithelial glands ducts were distributed throughout the ejaculatory sinuses, the prostate and coagulation gland ducts did not open in these sinuses. The urethra was composed of transitional epithelium, while the ejaculatory sinuses were composed of single to stratified cuboidal epithelium. The ejaculatory ducts continued to the ejaculatory ostium in male adult Sprague-Dawley rat were composed of the seminal vesicle ducts received the ampullary gland ducts. [ABSTRACT FROM AUTHOR]

Abstract Background The levels and immunohistochemical localization of muscle carbonic anhydrase III (CA-III) in healthy chickens and in muscular dystrophia affected (DA) chickens show that the muscles of diseased animal undergo a progressive increase of enzyme activity. Methods An enzyme-linked immunoassay was used to assess the CA-III levels in the muscles and other tissues from eight normal White Leghorn chickens and in two chickens with muscular dystrophy. Immunohistochemical localization of the enzyme in the muscles of these animals was also determined. Results The levels of CA-III in the tensor fasciae latae and the superficial pectoral muscles of the DA chickens were higher than the level in normal chickens. The concentrations of CA-III in erythrocytes and plasma from diseased chickens were approximately 15-fold and 1.4-fold higher than in the normal chickens, respectively. In the superficial pectoral and the tensor fasciae latae muscles of diseased chickens, the numbers of strongly stained and weakly stained fibers were greater than that in the normal chickens. Conclusion The levels of CA-III in the superficial pectoral muscle, the tensor fasciae latae muscle, plasma and erythrocytes from the chickens with muscular dystrophy were higher than found in normal chickens.

Abstract Background Carbonic anhydrase (CA) of the chicken has attracted attention for a long time because it has an important role in the eggshell formation. The developmental profile of CA-II isozyme levels in chicken erythrocytes has not been determined or reported. Furthermore, the relations with CA-II in erythrocyte and egg production are not discussed. In the present study, we isolated CA-II from erythrocytes of chickens and determined age-related changes of CA-II levels in erythrocytes. Methods Chicken CA-II was purified by a combination of column chromatography. The levels of CA-II in the hemolysate of the chicken were determined using the ELISA system in blood samples from 279 female chickens, ages 1 to 93 weeks, 69 male chickens, ages 3 to 59 weeks and 52 weeks female Araucana-chickens. Results The mean concentration of CA-II in hemolysate from 1-week-old female was 50.8 ± 11.9 mg/g of Hb. The mean levels of CA-II in 25-week-old (188.1 ± 82.6 mg/g of Hb), 31-week-old (193.6 ± 69.7 mg/g of Hb) and 49-week-old (203.8 ± 123.5 mg/g of Hb) female-chickens showed the highest level of CA-II. The levels of CA-II in female WL-chickens significantly decreased at 63 week (139.0 ± 19.3 mg/g of Hb). The levels of CA-II in female WL-chicken did not change from week 63 until week 93.The mean level of CA-II in hemolysate of 3-week-old male WL-chickens was 78.3 ± 20.7 mg/g of Hb. The levels of CA-II in male WL-chickens did not show changes in the week 3 to week 59 timeframe. The mean level of CA-II in 53-week-old female Araucana-chickens was 23.4 ± 1.78 mg/g of Hb. These levels of CA-II were about 11% of those of 49-week-old female WL-chickens. Simple linear regression analysis showed significant associations between the level of CA-II and egg laying rate from 16 week-old at 63 week-old WL-chicken (p < 0.01). Conclusions Developmental changes and sexual differences of CA-II concentration in WL-chicken erythrocytes were observed. The concentration of CA-II in the erythrocyte of WL-chicken was much higher than that in Araucana-chicken (p < 0.01).

Amphotericin B deoxycholate (AMPH-B) is a polyene macrolide with antifungal activity. Liposomal AMPH-B (L-AMB) was developed to reduce side effects while maintaining antifungal activity. This study was aimed at evaluating and comparing the adverse event profiles of AMPH-B and L-AMB using a spontaneous reporting system. We analyzed the adverse event reports of AMPH-B and L-AMB from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Case report counts of adverse events were generated according to the preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA). Standardized MedDRA queries (SMQs) and system organ classes (SOCs) were used to compare the organ-specific adverse event profiles of AMPH-B and L-AMB. The reporting odds ratio and proportional reporting rate were used to detect pharmacovigilance signals. The FAERS database contains 21,173,818 cases from January 2004 to March 2024. Adverse events were reported in 2438 cases receiving AMPH-B treatment and 3344 cases receiving L-AMB treatment, including 848 and 1591 cases receiving intravenous AMPH-B and L-AMB injections, respectively. The most frequently reported drug-related adverse event in the AMPH-B and L-AMB groups was hypokalemia. SOCs with statistically significant differences were "Inv" (laboratory tests), "Resp" (respiratory, thoracic, and mediastinal disorders), "Genrl" (general and systemic disorders and conditions at the site of administration), "Card" (cardiac disorders), and "Blood" (blood and lymphatic system disorders). No statistically significant difference was observed in the SMQ profile of adverse events in "Renal" (renal and urinary disorders) and "Hepat" (hepatobiliary disorders) between the L-AMB and AMPH-B formulations in this study. Based on real-world data from FAERS, adverse event profiles of AMPH-B and L-AMB were compared. No statistically significant difference was observed in the SMQ profile of adverse events in the renal and hepatic SOCs between the L-AMB and AMPH-B formulations. Our results suggest that L-AMB is more tolerated by the kidneys than AMPH-B., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The authors disclose the receipt of the following financial support for the research, authorship, and/or publication of this article. This research was partially supported by JSPS KAKENHI,Grant Numbers 23H05264, 21K11100, and 21K06646. The funders played no role in the study design, data collection and analysis, decision to publish this article, or article preparation. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nokura et al.)

Three-dimensional (3D)-printed models of bones are a convenient and durable alternative to real bone specimens, and they have been used in anatomy laboratories. It is necessary to identify the precise advantages of 3D-printed models from all perspectives; not only the improvement in students' knowledge of anatomy but also the students' assessment of such models. Here, students of veterinary medicine and animal science evaluated the reproducibility and effectiveness of 3D-printed models as a learning tool by completing our questionnaires, with a focus on their understanding of the skull-morphological differences among dog breeds. With the COVID-19 pandemic having obliged veterinary universities to provide courses online, we also investigated how the pandemic affected the students' evaluation of the 3D-printed models. The questionnaire results revealed that the animal science students were satisfied with the reproducibility of the 3D-printed models, but the veterinary students were not (they preferred to use real specimens). The skull differences were well understood by both types of students, indicating that 3D-printed models are effective for learning about rare skeletal specimens. The veterinary students who experienced the COVID-19 pandemic tended to choose real specimens more often than those who did not have this experience. Our results suggest that the use of 3D-printed models as an introduction and the use of real specimens in anatomy laboratory courses can be adequate for veterinary students. Together our findings suggest ways to improve the educational performance of 3D-printed models for veterinary students who need to understand the anatomy of many species.

Introduction In neuropsychiatric pharmacotherapy, neuroleptic malignant syndrome (NMS) is a potentially serious side effect of antipsychotics characterized primarily by fever, disorientation, extrapyramidal disorders, and autonomic nervous system imbalance, which can lead to death if left untreated. We visualized the NMS profile of antipsychotics using a self-organizing map (SOM). We combined it with decision tree analysis to discriminate between 31 antipsychotics in more detail than typical antipsychotic (TAP) and atypical antipsychotic (AAP) classifications. Method A total of 20 TAPs and 11 AAPs were analyzed. We analyzed NMS reports extracted from the Japanese Adverse Drug Event Report (JADER) database based on standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (Standardized MedDRA Queries (SMQ) code: 20000044, including 68 preferred terms). The SOM was applied using the SOM package in R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results The Japanese Adverse Drug Event Report (JADER) database contained 887,704 reports published between April 2004 and March 2024. The numbers of cases of NMS (SMQ code: 20000044) reported for risperidone, aripiprazole, haloperidol, olanzapine, and quetiapine were 1691, 1294, 1132, 1056, and 986, respectively. After the antipsychotics were classified into six units using SOM, they were adapted for decision tree analysis. First, 31 antipsychotics branched off into groups with loss of consciousness, with one group (10 TAPs) consisting entirely of TAPs, and the other consisting of antipsychotics that were further separated into two groups with coma induced by TAPs and AAPs. Conclusion The results of this study provide a reference for healthcare providers when predicting the NMS characteristics induced by each drug in patients, thereby facilitating the effective treatment of schizophrenia., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This research was partially supported by JSPS KAKENHI Grant Number, 21K06646 and 21K11100. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Miyasaka et al.)

Background: Selective sinus replacement seems a reasonable option in cases requiring replacement of one or two sinuses of Valsalva, especially with acute aortic dissection and high bleeding risk., Methods: Six patients (average age 58±17 years;five males) underwent selective replacement of the right sinus of Valsalva with right coronary artery bypass grafting (n=5) in 2015-2023. Five patients developed acute aortic dissection and one developed aneurysm of the right sinus of Valsalva., Results: All patients survived the operation, and there were no cases requiring re-exploration for bleeding. Intraoperative transesophageal echocardiography showed trivial or less aortic regurgitation (AR) in all patients. Cardiopulmonary bypass time, aortic cross-clamping time, and lower body circulatory arrest time were 214±28 min, 159±22 min, and 31±6 min (n=5), respectively. During follow-up of 55±44 (4-104) months, all patients were asymptomatic. AR was mild or less in four patients, mild-moderate in one patient, and severe in one patient. All patients had normal cardiac function without left ventricular enlargement, and so no reoperation was required., Conclusions: Although this method appears to be relatively safe and effective, some patients developed late AR. Long-term follow-up of larger numbers of patients will be necessary to confirm its effectiveness.

With the coronavirus disease 2019 (COVID-19) pandemic, there is growing interest in utilizing adaptive platform clinical trials (APTs), in which multiple drugs are compared with a single common control group, such as a placebo or standard-of-care group. APTs evaluate several drugs for one disease and accept additions or exclusions of drugs as the trials progress; however, little is known about the efficiency of APTs over multiple stand-alone trials. In this study, we simulated the total development period, total sample size, and statistical operating characteristics of APTs and multiple stand-alone trials in drug development settings for hospitalized patients with COVID-19. Simulation studies using selected scenarios reconfirmed several findings regarding the efficiency of APTs. The APTs without staggered addition of drugs showed a shorter total development period than stand-alone trials, but the difference rapidly diminished if patient's enrollment was accelerated during the trials owing to the spread of infection. APTs with staggered addition of drugs still have the possibility of reducing the total development period compared with multiple stand-alone trials in some cases. Our study demonstrated that APTs could improve efficiency relative to multiple stand-alone trials regarding the total development period and total sample size without undermining statistical validity; however, this improvement varies depending on the speed of patient enrollment, sample size, presence/absence of family-wise error rate adjustment, allocation ratio between drug and placebo groups, and interval of staggered addition of drugs. Given the complexity of planning and implementing APT, the decision to implement APT during a pandemic must be made carefully., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Background: Acute generalized eruptive pustulosis (AGEP) is a rare, but serious, drug-related adverse event. This study aimed to determine the relationships between AGEP and age, sex, primary disease, and prescription medications using a database of adverse drug events, namely, the Japanese Adverse Drug Event Report (JADER) database., Methods: In this retrospective observational study, we analyzed AGEP reports extracted from the JADER database based on the preferred term for AGEP (code 10048799). We evaluated the effects of causative drugs, underlying diseases, age, and sex. The association between AGEP and prescription drugs was analyzed using the reporting odds ratio and adjusted for covariates using multiple logistic regression. Association rule mining was performed to evaluate the correlation between each combination of factors and AGEP., Results: Between April 2004 and March 2023, 823,662 reports, including 869 reports on AGEP, were entered in the JADER database. The highest percentage of reports in each age group was in males aged <10 years, and clarithromycin was the most used drug in males aged <10 years. Nasopharyngitis was the most common reason for use, and Kawasaki disease was reported as a reason for use among males under 10 years of age, but not among females., Conclusions: In boys aged <10 years, attention should be paid to the occurrence of AGEP when prescribing clarithromycin and treating Kawasaki disease., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mitsuhiro Nakamura reports financial support was provided by 10.13039/501100001691Japan Society for the Promotion of Science. If there are other authors, they 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.)

Background: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment., Methods: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry., Findings: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes., Interpretation: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles., Competing Interests: Competing interests: DP and Dr EL are members of the Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resources Evaluation management committee. AB is funded by Wellcome. JS and MS are cofounders and shareholders of Epimed Solutions, a healthcare cloud-based analytics company. They are also supported in part by individual research grants from CNPq and FAPERJ. SB is the current chair, and MR is the past chair of the Finnish Intensive Care Consortium (both unpaid). DAD is unpaid chair of NICE foundation. NI's primary affiliation is the Department of Healthcare Quality Assessment, which is a social collaboration department at the University of Tokyo supported by National Clinical Database, Johnson & Johnson K.K., and Nipro corporation. BKTV is the National Coordinator for the Indian Registry of IntenSive care (IRIS) and is supported for 0.5 FTE by funding from the Wellcome Trust, UK. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, information on injectable anticancer drug use and additional fee for enhanced collaboration (AEC) and additional fee for specific drug management guidance 2 (ASD2) claims from the NDB Open Data Japan (NODJ) dataset and the number of patients with cancer according to sex and age from the National Cancer Registry (NCR) dataset were integrated and evaluated to determine the current status and challenges in pharmacist interventions for patients receiving cancer treatment. The NODJ data, including receipt data billed from 2020 to 2021, were obtained from the Ministry of Health, Labour and Welfare website. The use of injectable anticancer drugs decreased relative to the number of cancer patients aged ≥ 75 years compared to those aged < 75 years. Regarding injectable anticancer drug use, the number of AEC claims was similar between men and women, but the number of ASD2 claims was lower in men than in women. The number of times community pharmacists claimed their ASD2 was approximately 5% of the number of times hospital pharmacists claimed their AEC. This study revealed that several patients did not receive sufficient guidance from community pharmacists compared to hospital pharmacists, suggesting a potential insufficiency in the collaboration between the two groups., Competing Interests: MI is an employee of Kifune Pharmacy. The other authors declare no conflicts of interest., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)