Evaluating the relationship between ocular blood flow and systemic organ blood flow in hemorrhagic shock using a rabbit model.

This study aimed to investigate the feasibility of utilizing noninvasive ocular blood flow measurements as potential indicators of systemic circulation in rabbits experiencing hemorrhagic shock. Using Laser speckle flowgraphy, ocular blood flow indices, relative flow volume (RFV), and mean blur rate in the choroidal area (MBR-CH) were assessed in New Zealand White rabbits (n = 10) subjected to controlled blood removal and return. Hemodynamic parameters and biochemical markers were monitored alongside ocular circulation during blood removal and return phases. Additionally, correlations between ocular parameters and systemic indices were examined. The results indicated that RFV and MBR-CH exhibited significant correlations with renal and intestinal blood flows, with stronger correlations observed during blood removal. Additionally, ocular blood flow changes closely mirrored systemic dynamics, suggesting their potential as real-time indicators of shock progression and recovery. These findings indicate that ocular blood flow measurements may serve as real-time indicators of the systemic circulation status during hemorrhagic shock, offering potential insights into shock management and guiding tailored interventions. Thus, noninvasive ocular blood flow evaluation holds promise as an innovative tool for assessing systemic circulation dynamics during hemorrhagic shock.

Unique genomic sequences in a novel Mycobacterium avium subsp. hominissuis lineage enable fine scale transmission route tracing during pig movement.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most prevalent mycobacteria causing non-tuberculous mycobacterial disease in humans and animals. Of note, MAH is a major cause of mycobacterial granulomatous mesenteric lymphadenitis outbreaks in pig populations. To determine the precise source of infection of MAH in a pig farm and to clarify the epidemiological relationship among pig, human and environmental MAH lineages, we collected 50 MAH isolates from pigs reared in Japan and determined draft genome sequences of 30 isolates. A variable number of tandem repeat analysis revealed that most pig MAH isolates in Japan were closely related to North American, European and Russian human isolates but not to those from East Asian human and their residential environments. Historical recombination analysis revealed that most pig isolates could be classified into SC2/4 and SC3, which contain MAH isolated from pig, European human and environmental isolates. Half of the isolates in SC2/4 had many recombination events with MAH lineages isolated from humans in East Asia. To our surprise, four isolates belonged to a new lineage (SC5) in the global MAH population. Members of SC5 had few footprints of inter-lineage recombination in the genome, and carried 80 unique genes, most of which were located on lineage specific-genomic islands. Using unique genetic features, we were able to trace the putative transmission route via their host pigs. Together, we clarify the possibility of species-specificity of MAH in addition to local adaptation. Our results highlight two transmission routes of MAH, one exposure on pig farms from the environment and the other via pig movement. Moreover, our study also warns that the evolution of MAH in pigs is influenced by MAH from patients and their residential environments, even if the MAH are genetically distinct.

The role of arterial stiffness in the onset of Takotsubo cardiomyopathy observed with noradrenaline administration and intracranial blood injection in rabbits.

Takotsubo cardiomyopathy (TCM) has been reported to occur after subarachnoid hemorrhage, and the involvement of a critical activity of catecholamines has been mentioned, but the details of its onset have not been fully clarified. Recently, proper arterial stiffness could be measured with cardio-ankle vascular index. Therefore, we aimed to clarify the role of arterial stiffness in onset of TCM using rabbits under infusion of noradrenaline and injection of blood into brain ventricle. Rabbits were divided into three groups: infusion of noradrenaline (group A), infusion of noradrenaline + injection of saline into the brain ventricle (group B), infusion of noradrenaline + injection of blood in the brain ventricle (group C). Aortic arterial stiffness beta (Aß) and femoral arterial stiffness beta (Fß) were defined according to definition of the cardio-ankle vascular index. Blood pressure (BP), Aß, Fß, and femoral vessel resistance (FVR) were measured. Left ventricular movement were monitored with echocardiography. BP increased uniformly in all three groups. Fß in the group A, B and C increased from 3.6 ± 3.2, 3.6 ± 3.6 and 3.9_ ± 4.2 to 15 ± 2, 17.9 ± 2.4, 34.8 ± 9.1 due to the ICP enhancements in addition to noradrenaline administration, respectively. Fß in groups B and C was significantly larger than that in group A. On echocardiography, a much higher akinesic area of the apex was observed in group C compared with group A and B. Cardiac movements similar to TCM were observed slightly in group B and definitely in group C. Noradrenaline administration infusion and blood injection into the brain ventricle induced TCM accompanying with enhanced femoral arterial stiffness. These results suggested that elevated arterial stiffness might be involved in the formation of TCM in addition to a critical activity of catecholamines and an increase in intracranial pressure with blood injection.

Real-Time Evaluation of Regional Arterial Stiffening, Resistance, and Ocular Circulation During Systemic Administration of Adrenaline in White Rabbits.

Purpose: To evaluate continuous variations of ocular microcirculation by laser speckle flowgraphy and those of regional stiffening by pulse wave velocity (PWV) and vascular resistance under systemic adrenaline administration in rabbits. Methods: Six 16-week-old male rabbits were evaluated. The mean blur rates in the retinal vessel (MBR-RV) and choroid (MBR-CH) were measured. We assessed blood pressure (BP), femoral and carotid vascular resistance, and the heart-ankle (ha)-PWV, heart-femoral (hf)-PWV, and femoral-ankle (fa)-PWV. Adrenaline (100, 300, and 1000 ng/kg) was intravenously administered over a 10-minute period during which the parameters were measured simultaneously every 2 minutes. Results: The MBR-RV and MBR-CH values were dose-dependently increased by the adrenaline in parallel with increased BP. At the load of 100 ng/kg adrenaline, the ΔMBR-RV and ΔMBR-CH showed positive correlations with the variation rate in mean arterial blood pressure. Also, the variation rate in carotid vascular resistance and the Δfa-PWV and Δhf-PWV were significantly positively correlated with both the ΔMBR-RV and ΔMBR-CH. At the 300-ng/kg phase, the correlations between the Δha-PWV and both ΔMBR-RV and ΔMBR-CH were canceled; instead, the Δhf-PWV showed a significant negative correlation with the ΔMBR-RV and ΔMBR-CH. At the 1000-ng/kg phase, Δha-PWV again showed significant positive correlations with the ΔMBR-RV and ΔMBR-CH. Conclusions: These results indicate the possibility that under a systemic administration of adrenaline in rabbits, not only the BP value but also the vascular resistance and arterial function are related to the variation in ocular microcirculation. Translational Relevance: A real-time evaluation system of systemic regional arterial function and ocular microcirculation in rabbits was developed.

Fatal suppurative meningoencephalitis caused by Klebsiella pneumoniae in two calves.

One calf died (No. 1) and another was euthanized following astasia (No. 2). Histopathological examination revealed suppurative meningoencephalitis in these calves. Klebsiella pneumoniae antigens were detected in lesions. Thymocytes were decreased in the thymus cortex in both cases. 16S rRNA gene sequencing of the No. 1 isolate and bacterial extracts from formalin fixed paraffin embedded sections of No. 2 revealed that both samples were K. pneumoniae. The No. 1 isolate showed multidrug resistance against penicillin antibiotics, fosfomycin, streptomycin, macrolide antibiotics, tetracycline antibiotics, and clindamycin. Immunosuppression is a significant septicemic K. pneumoniae infection risk factor. Our study provides new aspects regarding K. pneumoniae infections in cattle, bacterial meningoencephalitis differentiation, and K. pneumoniae and bacterial meningoencephalitis treatments.

The influence of hemorrhagic shock on ocular microcirculation by obtained by laser speckle flowgraphy in a white rabbit model.

PURPOSE: To clarify the continuous changes in the retinal vessels' and choroid's microcirculation during hemorrhagic shock and resuscitation in a rabbit model. METHODS: Hemorrhagic shock by the removal of blood (30 mL) and resuscitation by a blood-return technique was induced in anesthetized male New Zealand White rabbits (n = 10). We evaluated the retinal vessel blood flow (relative flow volume: RFV) and choroidal blood flow (mean blur rate in the choroid area: MBR-CH) by laser speckle flowgraphy (LSFG), with simultaneous measurements of systemic hemodynamics and laboratory parameters. RESULTS: RFV and MBR-CH showed significant decreases immediately after the initiation of blood removal and recovered by blood return. The lactate concentration tended to increase from baseline by the blood-removal operation, and it was significantly higher at the end of observation period. The %RFV and %MBR-CH each showed a significant positive correlation with mean arterial blood pressure, cardiac output, carotid blood flow, and central venous pressure. %RFV showed a significant positive correlation with %central venous oxygen saturation and negatively correlated with %lactate. The %hemoglobin did not show a significant correlation with %RFV or %MBR-CH. CONCLUSION: This rabbit hemorrhagic shock model confirmed that ocular microcirculation measurements by LSFG feasibly reflect variations in systemic hemodynamics during hemorrhagic shock and recovery.

The relationship between the quantitative evaluation of thyroid bed uptake and the disappearance of accumulation in adjuvant radioactive iodine therapy for differentiated thyroid cancer.

OBJECTIVE: Iodine-131 (I-131) radioactive iodine therapy (RAI) after total thyroidectomy is the standard treatment for patients with differentiated thyroid cancer (DTC). We investigated the relationship between the quantitative parameters of the iodine uptake and the disappearance of the accumulation in the thyroid bed in adjuvant therapy using a 1.11 GBq or 3.70 GBq dose of I-131. METHODS: We retrospectively analyzed the cases of 40 patients with DTC who were treated with RAI at our institution between April 2017 and August 2019. The patients were treated with the I-131 dose of 1.11 GBq (n = 25) or 3.70 GBq (n = 15) after total thyroidectomy. The I-131 whole-body scan and hybrid single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) were performed 3 days after RAI. Using image analysis software, we measured the standardized uptake value (SUV) and absolute radioactivity concentration (kBq/ml) on the target lesions with the highest uptake in the thyroid bed. RESULTS: The median period from RAI to the evaluation of the absence of uptake of the thyroid bed was 6.75 months. After RAI, uptake of the thyroid bed disappeared in 26 of the 40 patients. The disappearance rate was significantly higher in the 3.70 GBq group than in the 1.11 GBq group (86.7% vs. 52.0%, respectively; p = 0.029). However, there were no significant differences in the values of kBq/ml or SUV between the 1.11 GBq group and 3.70 GBq group. On the other hand, the group in which the uptake disappeared after RAI showed significantly higher kBq/ml max and kBq/ml mean values than the group in which the uptake did not disappear after RAI (p = 0.028, p = 0.032, respectively). The SUVmax and SUVmean also tended to be higher in the disappeared-uptake group than the not-disappeared-uptake group, but the differences were not significant (p = 0.166, p = 0.176, respectively). CONCLUSIONS: The quantitative evaluation might be useful as one of the predictive indicators of the disappearance of the accumulation of radioactive iodine in the thyroid bed.

Genomic features of Mycobacterium avium subsp. hominissuis isolated from pigs in Japan.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most important agents causing non-tuberculosis mycobacterial infection in humans and pigs. There have been advances in genome analysis of MAH from human isolates, but studies of isolates from pigs are limited despite its potential source of infection to human. Here, we obtained 30 draft genome sequences of MAH from pigs reared in Japan. The 30 draft genomes were 4,848,678-5,620,788 bp in length, comprising 4652-5388 coding genes and 46-75 (median: 47) tRNAs. All isolates had restriction modification-associated genes and 185-222 predicted virulence genes. Two isolates had tRNA arrays and one isolate had a clustered regularly interspaced short palindromic repeat (CRISPR) region. Our results will be useful for evaluation of the ecology of MAH by providing a foundation for genome-based epidemiological studies.

Chronic pancreatitis in farmed pigs fed excessive zinc oxide.

Most of the pigs on a farm in Aichi Prefecture, Japan had chronic diarrhea and severe wasting. The pigs had consumed 8,000 ppm zinc oxide (ZnO) as a feed additive. The pancreas of each of 4 autopsied pigs was less than half the normal size. Acinar cells were considerably decreased. Epithelial duct-like cells were increased and tested positive for cytokeratin AE1/AE3, Ki67, PGP9.5, and Sox9. Pancreatic islet cells were decreased and shrunken. The α and δ cells were relatively decreased, and their distribution was abnormal. Islet cells were positive for PGP9.5. The livers and kidneys had high accumulations of zinc (Zn; 788 µg/g and 613 µg/g, respectively). Copper was deficient in the liver, likely as a result of Zn poisoning. Our immunohistologic examination suggested that the high dose of ZnO could influence the function of islet cells in addition to that of acinar cells. Given that colistin sulfate has been banned as a feed additive in order to reduce antimicrobial use in Japan, the use of ZnO in the livestock industry is expected to increase. Zn supplementation of pig feed must be monitored to prevent Zn poisoning and contamination of soil and water.

Inclusion body hepatitis caused by Aviadenovirus in a tropical screech owl (Megascops choliba).

In 2016, tropical screech owl (Megascops choliba) (Tso) chicks were suddenly found dead in a Japanese breeding facility. We autopsied a 9-day-old Tso and discovered white spots scattered on the liver surface. Multifocal necrosis was diffused, and macrophages had infiltrated the necrotic hepatic lesions. Hepatocytes contained numerous intranuclear inclusion bodies. Immunohistochemical staining detected Adenovirus antigen only in the liver. Next, PCR and sequencing (LC536616) identified Tso Adenovirus (TsoAd). Basic Local Alignment Search Tool (BLAST) and phylogenic analyzes suggested TsoAd is an owl Aviadenovirus. Our study contributes to an improved understanding of infectious disease among captive raptors.

[Clinical Complete Response to Definitive Chemoradiotherapy for Advanced Lower Rectal Cancer-A Case Report].

A man in his 80s was admitted to our hospital with a chief complaint of bloody stools. He was diagnosed with cT2N0M0, cStage Ⅰ rectal cancer. As the patient was of advanced age and had multiple comorbidities, definitive chemoradiotherapy was administered. Immediately after treatment, the patient achieved a complete clinical response, and recurrence has not been detected for 2 years and 3 months since treatment.

Pyelonephritis caused by Mannheimia varigena in a Holstein calf.

A 7-day-old calf died following development of mild respiratory symptoms. Postmortem examination revealed the kidneys were inflamed, and Gram-negative bacteria was detected in the kidneys, supporting the diagnosis of suppurative pyelonephritis. Mannheimia varigena antigen was found in the lesions and the cytoplasm of macrophages and neutrophils in the renal cortex. The Gram-negative bacilli from the kidney were identified as M. varigena by sequencing the 16S rDNA. Although M. varigena is known to cause bovine respiratory disease syndrome, shipping fever, and meningitis, it was unknown that it could also cause suppurative pyelonephritis. Our study provides the first evidence of suppurative pyelonephritis caused by M. varigena in cattle and information that would improve our understanding, diagnosis, and treatment for M. varigena infections.

Angiotensin II acutely increases arterial stiffness as monitored by cardio-ankle vascular index (CAVI) in anesthetized rabbits.

The cardio-ankle vascular index (CAVI) has been established as a stiffness indicator from thoracic aorta to tibial arteries. To better understand physiological regulatory factors for the arterial stiffness, we assessed effects of angiotensin II and adrenaline on the CAVI in anesthetized rabbits. A hypertensive dose of angiotensin II (300 ng/kg, i.v.) increased the CAVI as well as the heart-ankle pulse wave velocity (haPWV). On the other hand, although a hypertensive dose of adrenaline (1000 ng/kg, i.v.) increased the haPWV, it did not affect the CAVI. These results suggest that angiotensin II may act as a regulatory factor for arterial stiffness.

Draft genome sequences of Mycolicibacterium peregrinum isolated from a pig with lymphadenitis and from soil on the same Japanese pig farm.

OBJECTIVES: Mycolicibacterium peregrinum, a rapidly growing mycobacterial species, can opportunistically infect humans and other animals. Although M. peregrinum infections in animals have been reported, the infection sources are unknown, as is information on its virulence and drug resistant genes, which limits our current understanding of this bacterium. To address this knowledge gap, we obtained draft genome sequences for two M. peregrinum isolates; one from a case of pig lymphadenitis and one from the pig farm's soil. DATA DESCRIPTION: We report here the draft genome sequences of M. peregrinum isolates 131_1 and 138 (6,451,733-bp and 6,479,047-bp). They were isolated from a pig with mesenteric lymph node lymphadenitis and from soil on the Japanese farm where the pig was reared. A sequence alignment identity score of 100% was obtained by in silico DNA-DNA hybridization of the two isolates, while 98.28% (isolate 131_1) and 98.27% (isolate 138) scores were recorded for hybridization with a human isolate. Both isolates carry arr-1, AAC(2')-Ib, RbpA, mtrA and tap drug-resistance genes. Isolates 131_1 and 138 carry 234 and 236 putative virulence genes, respectively. Therefore, environment M. peregrinum is potentially drug resistant and can cause swine lymphadenitis. Our data provides valuable new information for future studies on nontuberculous mycobacteria.

Quality of life after external beam radiotherapy for localized prostate cancer: Comparison with other modalities.

In external beam radiotherapy for localized prostate cancer, acute toxicities are typically transient and mild. These symptoms will disappear within 4-8 weeks after external beam radiotherapy. Some patients might suffer from proctitis with bloody stools as late rectal toxicity. Therefore, it has been shown that external beam radiotherapy has a more pronounced negative impact on bowel function compared with other treatment modalities. However, the recent development of modern beam delivery techniques, including intensity-modulated radiotherapy, allows us not only to deliver higher doses to the prostate, but also to decrease the doses to the critical organs, resulting in the maintenance of patients' quality of life within satisfactory levels. Patients' quality of life after external beam radiotherapy is also strongly related to the total dose, fractionation regimens, dose parameters of the critical organs and treatment plan quality, with a trade-off between the radicality of external beam radiotherapy and potentially increased toxicity. Radiation oncologists should choose treatment parameters carefully to achieve a reasonable balance between a good oncological outcome and the patient's quality of life.

Septicemic Actinobacillus suis infection in a neonatal piglet with multifocal necrotic glossitis.

Five-day-old neonatal piglets presented with debilitation and ananastasia. At the necropsy of one piglet, the apex of the tongue was found to be discolored dark red, and disseminated white foci were found on the cut surface. Many white foci were also found in the lungs and on the serosa of the liver and spleen. Histopathological findings revealed multifocal necrotic glossitis and pneumonia with Gram-negative bacilli. The bacilli were identified as Actinobacillus suis through immunohistochemical, biochemical, and genetic tests, including 16S rRNA gene sequencing. Although A. suis usually causes inflammation in thoracic and abdominal organs, lesions were also found in the tongue in the present case. This study is the first report of glossitis caused by A. suis.

Radiation-induced sarcoma after radiation therapy for prostate adenocarcinoma.

INTRODUCTION: Radiation therapy is widely used for prostate cancer, but radiation-induced sarcomas have been rarely reported. CASE PRESENTATION: A 77-year-old Japanese male was diagnosed with prostate cancer and received a combined androgen blockade and radiation therapy (total dose of 76 Gy). Five years after the radiation therapy, testicular pain and dysuria appeared. Computed tomography showed a soft tissue dense mass with invasion to the right subpubic ramus and prostate, mainly to the perineum. A needle biopsy revealed the pathological features of high-grade sarcoma. The patient was diagnosed with radiation-induced sarcoma based on the cancer's occurrence in the vicinity of the radiation field. CONCLUSION: Although irradiation is one of the important treatments for prostate cancer, the risk of radiation-induced malignancy should be considered.

Physiological role of nitric oxide for regulation of arterial stiffness in anesthetized rabbits.

We assessed effects of acetylcholine and Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME) on the cardio-ankle vascular index (CAVI), an indicator of arterial stiffness from origin of aorta to tibial artery, in halothane-anesthetized rabbits. Acetylcholine decreased the blood pressure, femoral vascular resistance and CAVI, whereas l-NAME did not affect the CAVI at a hypertensive dose. The acetylcholine-induced decrement of CAVI was completely suppressed by l-NAME. These results suggest that the arterial stiffness in rabbits may be independent from homeostatic production of nitric oxide, however, it can be decreased by large amounts of nitric oxide that are intrinsically produced by exogenously administered acetylcholine.

Bovine vegetative endocarditis caused by Streptococcus suis.

A 5-month-old crossbred beef steer died after exhibiting astasia. A postmortem examination revealed verrucous endocarditis and numerous renal hemorrhages. Gram-positive bacteria were identified in the necrotic lesions of the verruca and mitral valve via histopathological analysis. Multifocal necrosis and hemorrhage were detected in the renal cortex. Gram-positive cocci isolated from the verruca were identified via biochemical tests and 16S rRNA gene sequence analysis as Streptococcus suis. Serotyping indicated that the S. suis isolates were untypable, following which these isolates were classified as a new sequence type (ST1000) via multi-locus sequence typing. S. suis is an important pathogen of pigs. However, clinical cases in cattle are rare. This report is intended to provide information that may be useful in the diagnosis of streptococcal disease in cattle.

Combined radiotherapy with nivolumab for extracranial metastatic malignant melanoma.

PURPOSE: We retrospectively evaluated the tumor regression after radiotherapy in combination with the immune checkpoint inhibitor nivolumab for metastatic melanoma. MATERIALS AND METHODS: We evaluated the extracranial metastatic melanoma lesions to which concomitant radiotherapy with nivolumab was administered from June 2015 to February 2017. Tumor volume and maximum diameter were measured at the time of pre-radiotherapy and best response, and the tumor reduction rate was assessed in two ways that our hospital adopts: tumor volume and diameter. RESULTS: Seven lesions in five patients were evaluated. The median time from the start of nivolumab treatment to the start of radiotherapy was 5 months (range 0-22 months). The objective response rate was 85.7% in the evaluation by tumor volume and 42.9% by maximum diameter of the tumor. The objective complete response rate was 28.6% in evaluation by tumor volume and 14.3% by maximum dia. The 1-year tumor control rate was 62.5%. The 1- and 2-year overall survival rate after nivolumab treatment were 75% and 50%, respectively. Two patients who obtained a complete response had presented with vitiligo. CONCLUSION: The combination of radiotherapy and nivolumab treatment produced favorable responses. Vitiligo may be correlated with a good response to concomitant radiotherapy with nivolumab.