Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial.

BACKGROUND: Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. METHODS: An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MES of 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. RESULTS: The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). CONCLUSIONS: Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.

Dose escalation of 5-aminosalicylic acid for ulcerative colitis reduced relapse rate in patients in clinical remission with a Mayo endoscopic subscore of 1. The therapeutic efficacy was more evident in those whom immunomodulators were used.

Clinical outcomes of patients with remitting ulcerative colitis after discontinuation of indigo naturalis.

Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

Medical records as screening tools for child death review in Japan.

BACKGROUND: Although many child death review (CDR) systems have been developed in Japan, the optimal system is still being identified. The aim of this study is to identify the etiologies of child deaths and to propose a screening method for initiating the CDR process in Japan. METHODS: Clinical medical records (CMRs) in hospitals and autopsy records were surveyed for cases of deaths of children aged less than 15 years between 2014 and 2016 in Aichi Prefecture, Japan. The data were analyzed in three steps, and the findings were compared with the vital statistics. RESULTS: Of the 695 children whose death certificates were submitted to Aichi Prefecture, 590 could be traced to pediatric care hospitals. The distribution of causes of death was slightly different from the vital statistics, with 11.5% dying of extrinsic causes and 19.7% dying of unknown causes. Maltreatment was suspected in 64 cases, which was much higher than that in government statistics. Overall, 158 (26.8%) deaths were considered preventable. The number of unnatural deaths, which might be screened in, was calculated as 172 (29.2%) in the vital statistics, whereas the survey of CMRs revealed that 241 (40.8%) to 282 (47.8%) should be screened in. CONCLUSIONS: Surveying CMRs in hospitals may be a suitable method to detect and screen deaths to start the CDR process in Japan.

A lethal case of massive hemorrhage after percutaneous liver biopsy in a patient with thrombasthenia.

Percutaneous needle liver biopsy is an important procedure in the diagnosis of and assessment of the severity of liver diseases. Although liver biopsy is considered to be a relatively safe procedure, there are occasional cases of death due to massive bleeding after liver biopsy. Thrombasthenia is a disease in which bleeding occurs in the mucosa and skin due to platelet dysfunction. A 60-year-old female was admitted for a liver biopsy for further investigation after an abnormal liver function test. She was diagnosed with thrombasthenia and was being treated with oral tranexamic acid and carbazochrome. Blood tests showed little decrease of platelet count and no abnormalities of blood coagulability. Approximately ten hours after the liver biopsy, the patient complained of nausea and lightheadedness, followed by decreased blood pressure and decreased consciousness. An emergent abdominal CT scan showed a large amount of blood in the abdominal cavity. The patient died despite multidisciplinary treatment, and a forensic autopsy was performed. At internal examination, approximately 2,620 mL of dark red blood was accumulated in the abdominal cavity. A puncture wound led 1.8 cm into the liver from the surface of the liver, and no major vascular damage was observed. The cause of death was considered to be blood loss due to bleeding from the puncture wound. Even if the platelet count is normal, such as in a case of thrombasthenia, the risk of bleeding should not be underestimated. Careful attention should be paid when performing liver biopsy in a patient with risk factors.

Cadavers found outdoor in whom fungal growth was observed on the body surface: Consideration of the role of mycology in forensic medicine.

In forensic case work, fungal growth is occasionally observed on decomposed cadavers, however, the isolation of these organisms is not always carried out routinely. The usefulness of investigating fungi isolated from corpses in forensic settings, has been reported, such as providing trace evidence, estimating the time since death, and ascertaining the time of deposition. A 32-year-old male missing for 4 months, was found in a car in a forest far from his home and had died from blood loss, having been stabbed with a kitchen knife in the left side of his chest. Whitish or white greenish colonies ranging 5 cm to 8 cm in size were observed over his whole body. Penicillium commune and Cladosporium cladosporioides were isolated from the colonies. A 49-year-old male missing for one month, and was found dead at 500 m elevation in the mountains. An autopsy was conducted, but the cause of death could not be determined. Dark greenish or whitish colonies were found on his face and neck, and Epicoccum nigrum, Mucor sp.. Cladosporium sp., and Pestalotiopsis sp. were isolated. Penicillium sp. and Cladosporium sp. are major indoor fungi, and Epicoccum sp. and Pestalotiopsis sp. are plant pathogens found in outdoor environments. There was no discrepancy between the police statement and findings of the corpse such as place discovered, types of isolated fungi, and estimated time since death. Identifying fungi on cadavers may aid in forensic casework, and further studies are needed to develop for the use of fungi as a forensic tool.

Plasma membrane damage triggered by benzalkonium chloride and cetylpyridinium chloride induces G0/G1 cell cycle arrest via Cdc6 reduction in human lung epithelial cells.

Quaternary ammonium compounds, including benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC), are widely used as disinfectants. Increased use of inhalable products containing BAC or CPC has raised concerns for lung toxicity. This study sought to elucidate the microstructure of plasma membrane damage caused by BAC and CPC and the subsequent mechanism by which the damage is mediated, as assessed using two human pulmonary epithelial cell lines (A549 and BEAS-2B). Scanning electron microscopic observation showed that exposure to BAC or CPC for 3 hr reduced the length and density of microvilli on the plasma membrane in A549 cells. Analysis of cell cycle distribution following plasma membrane damage revealed that BAC and CPC promote G0/G1 cell cycle arrest in both cell lines. The protein levels of Cdc6, an essential regulator of DNA replication during G1/S transition, are decreased significantly and dose dependently by BAC or CPC exposure. CPC and BAC decreased the Cdc6 levels that had been increased by a PI3K agonist in A549 cells, and levels of phosphorylated AKT were reduced in response to BAC or CPC. Conversely, exposure to equivalent concentrations of pyridinium chloride (lacking a hydrocarbon tail) induce no changes. These results suggest that plasma membrane damage triggered by BAC or CPC causes Cdc6-dependent G0/G1 cell cycle arrest in pulmonary cells. These effects are attributable to the long alkyl chains of BAC and CPC. The reduction of Cdc6 following plasma membrane damage may be caused, at least in part, by diminished signaling via the PI3K/AKT pathway.

Risk of venous thromboembolism with a central venous catheter in hospitalized Japanese patients with inflammatory bowel disease: a propensity score-matched cohort study.

BACKGROUND/AIMS: Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis. METHODS: This retrospective cohort study included patients with ulcerative colitis or Crohn's disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses. RESULTS: Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn's disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68-102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64-46.10). CONCLUSIONS: CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.

Usefulness of texture and color enhancement imaging in assessing mucosal healing in patients with ulcerative colitis.

BACKGROUND AND AIMS: Endoscopic remission is known to be defined as a Mayo endoscopic subscore (MES) of ≤1 in patients with ulcerative colitis (UC). However, some individuals experience relapse even after showing endoscopic remission under white-light imaging (WLI), and no tool exists that can detect these individuals. The aim of this study was to clarify the usefulness of texture and color enhancement imaging (TXI) in the assessment of inflammation in patients with UC. METHODS: This was a prospective, single-arm, observational study conducted at a university hospital. From January 2021 to December 2021, 146 UC patients with endoscopic remission were enrolled. Images were evaluated by WLI, TXI, and pathologic evaluation, followed by prognostic studies. The primary endpoint of the study was the cumulative relapse of UC in each TXI score. The secondary endpoints were the association between TXI and pathologic scores, predictors of relapse, and interobserver agreement between the MES and TXI scores. RESULTS: Patients with TXI score 2 had significantly lower UC relapse-free rates than did those with TXI scores 0-1 (log-rank test, P < .01). When pathologic remission was defined as Matts grade ≤2, the rate of pathologic remission decreased significantly with higher TXI scores (P = .01). In multivariate analysis, TXI score 2 was the only risk factor for UC relapse (P < .01; hazard ratio, 4.16; 95% confidence interval, 1.72-10.04). Interobserver agreement on the TXI score was good (κ = 0.597-0.823). CONCLUSION: TXI can be used to identify populations with poor prognosis in MES 1, for whom treatment intensification has been controversial.

Stability of exosomes in the postmortem serum and preliminary study on exosomal miRNA expression profiling in serum from myocardial infarction cadavers.

Exosome-encapsulated miRNAs could potentially be sensitive biomarkers of human diseases. Since a lipid bilayer membrane surrounds exosomes, the exosomal miRNA may stably exist in body fluids with diseases as well as biological fluids. Therefore, exosomal miRNA may be helpful for autopsy diagnosis. Assuming cadaver blood would be most useful, we initially examined serum exosome stability with regard to storage temperatures and periods. Characteristic analyses of the exosome revealed that exosomes and the content, miRNA, were stably preserved until at least three days when stored at below 20 °C. Subsequently, exosomal miRNA expression profiling was performed on the serum of acute myocardial infarction (AMI, 4 cases) autopsy bodies and on hemorrhagic shock bodies used as the control (CT, 3 cases). Results showed that significant twofold up- and downregulations of expression of 18 and 16 miRNAs were detectable in AMI as compared to the CT, respectively. miR-126-3p, which has been reported to be increased in serum of AMI patients and a mouse model, was one of the significantly upregulated miRNAs. Furthermore, dysregulation of exosomal miRNAs, such as miR-145-5p, miR-143-3p, and miR-222-3p, which are involved in cardioprotection, may be associated with AMI pathogenesis. These findings provide a novel perspective on the potential role of exosomal miRNA in determining the cause of death.

Effectiveness and Durability of Ustekinumab Therapy With or Without Immunomodulators for Ulcerative Colitis Patients in Japan.

Background and Aims: The effectiveness and durability of ustekinumab therapy with or without thiopurine immunomodulators (IMs) for ulcerative colitis (UC) in real-world Asian, Japanese patients have not yet been elucidated. Methods: To evaluate the additive effects of IMs on ustekinumab, a retrospective cohort study of UC patients receiving ustekinumab with or without thiopurine IMs, azathioprine or 6-mercaptopurine, was conducted from March 2020 to August 2021. The primary endpoint was clinical remission or response rate at week 8. The secondary endpoints were clinical remission or response rates at weeks 24 and 52, the durability of each treatment, and adverse events. Results: Of the 50 patients with UC treated with ustekinumab, 42 were enrolled. Sixteen patients were treated with a combination of ustekinumab and an IM. The clinical response rates of all patients at weeks 8, 24, and 52 were 53.7%, 63.3%, and 42.9%, respectively. There was no significant difference in the clinical responses or remission rates between the combination therapy and monotherapy groups at weeks 8, 24, and 52. (50.0% vs. 56.0%, P = .757; 70.0% vs. 60.0%, P = .702; and 42.9% vs. 42.9%, P = 1.00, respectively). A Kaplan-Meier analysis showed no difference in IM use on the durability of ustekinumab treatment (log-rank test; P = .955). Conclusions: The response rate for Japanese UC patients is similar to previous reports based on American and European UC patients. There was no significant difference between the ustekinumab monotherapy group and the ustekinumab and IM combination group in the real world.

Unique clinical phenotypes of patients with obstructive sleep apnea in a Japanese population: a cluster analysis.

STUDY OBJECTIVES: In an attempt to better understand the heterogeneity of individuals with obstructive sleep apnea (OSA), unbiased analytic approaches such as cluster analysis have been used worldwide; however, only a few such studies have been conducted for Asian populations alone, despite the potential racial/ethnic differences. We thus applied this approach to a Japanese population with OSA. METHODS: In this single-center, retrospective, observational study, our nocturnal polysomnography dataset included the findings for 1,020 patients between May 2016 and December 2020. Of these, 712 patients met the study criteria: aged > 20 years, fully completed questionnaire, no missing data on all-night full polysomnography, and confirmed OSA diagnosis with an apnea-hypopnea index (AHI) > 15 events/h. We employed hierarchical cluster analysis using demographic data, self-reported symptoms, and polysomnographic data. RESULTS: We identified 5 distinct clinical clusters within the OSA patient population, which were labeled as "classic OSA" (20--67 years, obese, high AHI, high Epworth Sleepiness Scale [ESS]), "milder classic OSA" (22--77 years, obese, high AHI, low ESS), "nonobese and minimally symptomatic" (20--88 years, moderate AHI, low ESS), "excessive sleepiness without severe OSA" (26--79 years, moderate AHI, high ESS), and "older adult and severe OSA" 55--92 years, (high AHI, low ESS). Of these, the last 3 clusters were characterized as nonobese. Notably, we identified the cluster with excessive sleepiness despite less severe OSA. We did not identify any clusters with predominant upper-airway obstruction symptoms because the symptoms were prevalent and equally distributed in all clusters. CONCLUSIONS: We found some unique clinical phenotypes in nonobese patients with OSA in a Japanese population. CITATION: Ida H, Suga T, Nishimura M, Aoki Y. Unique clinical phenotypes of patients with obstructive sleep apnea in a Japanese population: a cluster analysis. J Clin Sleep Med. 2022;18(3):895-902.

Epidemiology of child mortality and challenges in child death review in Japan: The Committee on Child Death Review: A Committee Report: The Committee on Child Death Review: A Committee Report.

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged <18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language.

Various Endoscopic Features in Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma.

A 77-year-old female who had an acute severe abdominal pain was taken to the emergency room in the previous hospital. CT scans showed jejunum and ileum wall thickening and fatty deposits around the small intestinal tract, and gastrointestinal perforation could not be ruled out. By using single anal and oral balloon endoscopy, we observed mild edema with petechial erythema, shallow erosions with edematous mucosa and ulcers with surrounded disrupted villous structures at the jejunum and ileum. Histological analysis revealed atypical lymphocytes infiltrating the small intestinal mucosa demonstrating intraepithelial lymphocytosis. Immunohistochemical staining revealed that CD3, CD7, and CD56 staining was positive, and CD4, CD5, and CD8 staining was negative in infiltrated lymphocytes. We made the diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) with the combination of HE staining and IHC. PET-CT showed abnormal uptake in irregular wall thickening of the small intestine, lymph nodes, ribs, spine and pelvic bone. She was treated with chemotherapy (etoposide, prednisolone, oncovin, cyclophosphamide, hydroxydaunorubicin) and is still alive 1 year after the diagnosis. We reported the various endoscopic findings in the same MEITL patient by using single balloon endoscopy. We also summarized endoscopic characteristics of MEITL patients.

An Autopsy Case of Spontaneous Coronary Artery Dissection With Eosinophilic Coronary Periarteritis and Degeneration of Medial Smooth Muscles.

ABSTRACT: A 45-year-old woman with no known medical history died suddenly shortly after complaining of anterior chest discomfort. The autopsy revealed a dissection at the anterior descending branch of the left coronary artery, and eosinophilic adventitial inflammation was observed both in the right coronary artery and in the vicinity of the dissection. Furthermore, there was degeneration of the tunica media in the right coronary artery, and this was thought to be a predissection lesion. In the degenerated area of the tunica media, probable apoptosis of smooth muscle cells was noted, suggesting that the degeneration was not due only to the effect of eosinophilic lytic enzymes. These findings also indicated that eosinophilic infiltration preceded the dissection. Eosinophilic infiltration around the coronary arteries is occasionally observed in cases of sudden death, but although it might be associated with the death, the pathological mechanism is yet to be elucidated. Eosinophilic periarteritis has also been observed around the site of spontaneous coronary artery dissection, although a causal relationship is unproven. The histopathology of this case indicated that the eosinophilic infiltration preceded the dissection. Detailed pathological findings are presented, together with a review of the literature.

Potential patient screening for late-onset Pompe disease in suspected sleep apnea: a rationale and study design for a Prospective Multicenter Observational Cohort Study in Japan (PSSAP-J Study).

BACKGROUND: Pompe disease is an autosomal recessive disorder caused by deficiency of the acid α-glucosidase (GAA) enzyme. GAA deficiency induces progressive glycogen accumulation which leads to weakness of the respiratory muscle including the diaphragm. Pompe disease is one of the few myopathies, for which an established therapy is available. Thus, earlier detection of potential late-onset Pompe disease (LOPD) and earlier intervention would have a significant clinical impact. PURPOSE: Our hypothesis is that sleep problems including sleep disordered breathing (SDB) and clinical symptoms may indicate an early stage of LOPD since decreased respiratory muscle activity generally first presents during sleep. Thus, the aims of this prospective, multicenter observational cohort study in Japan (PSSAP-J) are to demonstrate a higher prevalence of LOPD in a sleep lab-based population (primary outcome), and to identify predictive factors for LOPD from findings in diagnostic polysomnography (PSG) and clinical symptoms (secondary outcomes). METHODS: The study design is a prospective multicenter observational cohort study. Consecutive patients who present to sleep labs due to suspected SDB for an overnight PSG will be enrolled. All patients will be measured for creatine kinase, GAA activity, and if necessary, genetic analysis of GAA. Furthermore, chest X-ray, pulmonary function test, and arterial blood gas analysis will be collected. Then, prevalence and specific findings of LOPD will be assessed. RESULT: Congenital myopathy shows a shift from slow-deep to rapid-shallow breathing during transition from wakefulness to sleep accompanying a symptom of waking with gasping (actual further results are pending). DISCUSSION: The distribution in respiratory physiology between during wakefulness and sleep specific to LOPD may provide insights into early-stage detection. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000039191, UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ctr ).

Scavenger receptor MARCO contributes to cellular internalization of exosomes by dynamin-dependent endocytosis and macropinocytosis.

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor class-A protein that is expressed on the cell surface of macrophages. MARCO mediates binding and ingestion of unopsonized environmental particles, including nano-sized materials. Exosomes are cell-derived, nano-sized vesicles (40-150 nm) that can contain lipids, RNA, DNA, and various proteins. Exosomes play an essential role in cell-to-cell communication via body fluids. However, mechanisms for the recognition and internalization of exosomes by recipient cells remain poorly characterized. In this study, cellular association of serum-derived fluorescent exosomes and 20-nm fluorescent nanoparticles (positive control) was compared between MARCO-expressing (CHO-MARCO) and control (CHO-CT) CHO-K1 cells to examine whether MARCO expression by recipient cells mediates the cellular uptake of exosomes and environmental nanoparticles. Fluorescence microscopic studies and quantitative analyses revealed that the cellular associations of both exosomes and 20-nm nanoparticles were greater in CHO-MARCO cells than in CHO-CT cells. Exosomes and nanoparticles colocalized with green fluorescent protein (GFP)-MARCO in cells transfected with GFP-MARCO-encoding constructs . Furthermore, inhibitory studies showed that actin reorganization and dynamin are involved in the MARCO-mediated cellular internalization of exosomes. These results indicated that MARCO plays a role in the uptake of exosomes.

Effects of ear corn silage supplementation on milk production and milk fatty acid profiles in grazing dairy farms.

This study investigated the effects of substituting ear corn silage (ECS) for commercial formula feed on milk production and milk fatty acid profiles in grazing dairy farms during the summer season. A field survey was conducted on five grazing dairy farms in every summer month of 2017, 2018, and 2019. Three of the five farms substituted fresh ECS for the commercial formula feed at a ratio of 2:1 from July of each year (ECS farms). Other farms maintained the same feeding management as before (non-ECS farms). An interview survey was conducted on each farm to calculate feed intake and milk yield per cow. Feed and milk samples were collected in each survey. Milk compositions and milk fatty acid profiles were determined. The substitution of ECS for the commercial formula feed did not affect milk yield or milk composition, but ECS farms maintained low levels of milk urea compared with non-ECS farms (p < .01). The ECS substitution also influenced some of the milk fatty acid proportions; C16:0 and C16:1 increased, and trans-11 C18:1, cis-9,trans-11 C18:2, and the sum of polyunsaturated fatty acids decreased, while these fatty acid proportions were maintained in non-ECS farms throughout the summer season (p < .05).

Effects of feeding early-harvested orchardgrass-perennial ryegrass mixed silage instead of heading stage harvested timothy silage on digestion and milk production in dairy cows.

We evaluated the effects of replacement of heading stage harvested timothy silage with early-harvested orchardgrass-perennial ryegrass mixed (OP) silage while maintaining or reducing concentrate input on dry matter intake (DMI), milk production, nutrient digestibility, and N balance in dairy cows. Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design with three dietary treatments: TYL, a diet containing timothy silage where forage-to-concentrate ratio (FC) was 50:50; OPL, a diet containing OP silage where FC ratio was 50:50; and OPH, a diet containing OP silage where FC ratio was 60:40. We observed that an equal replacement of timothy with OP silage increased DMI, milk yield, milk protein production, and nutrient digestibility but decreased milk fat content (TYL versus OPL). We observed that replacing timothy with OP silage while reducing concentrate input increased milk fat and protein yield, nutrient digestibility, and feed efficiency and reduced urinary N loss with no effect on DMI or milk fat content (TYL versus OPH). These results show that replacing timothy with OP silage can be a good approach to improve milk production, feed efficiency, and N utilization and reduce concentrate input. However, milk fat depression should be considered when an equal substitution is performed.