Description of Discocotyle ciray n. sp. (Monogenea: Discocotylidae) from Parahucho perryi (Brevoort) from Hokkaido, Japan, with a redescription of D. sagittata (Leuckart, 1842).

Discocotyle sagittata (Leuckart, 1842) (Monogenea: Discocotylidae) is redescribed, based on specimens collected from the type host, Salmo trutta Linnaeus, from the type locality, Freiburg, Germany, supplemented with specimens from S. trutta and rainbow trout, Oncorhynchus mykiss (Walbaum) reared in an Austrian aquarium. The diagnosis of the genus Discocotyle Diesing, 1850 is emended. Discocotyle ciray n. sp. is described, based on immature, preadult and adult specimens from the salmonid, Parahucho perryi (Brevoort) at Eniwa, Hokkaido, Japan. Adult specimens of the new species were about twice as large as those of D. sagittata from S. trutta. When the type specimens of D. ciray n. sp. were examined together with museum specimens from P. perryi at Tsurui, Hokkaido, the body and clamp sizes were positively correlated to the host size. Their measurements from a smaller P. perryi at Tsurui overlapped with those of D. sagittata, showing that these size differences were not suitable differentiating keys. Discocotyle ciray n. sp. can be separated from D. sagittata by the morphologies of the female genital system (relatively anteriorly positioned ovary, short joint vaginal duct and much more strongly winding uterus). The genetic distances of COI mtDNA sequence between D. ciray n. sp. and D. sagittata were 18.0-18.6%. These remarkable genetic divergences also supported the distinct taxonomic status of D. ciray n. sp.

The beneficial effects of balloon pulmonary angioplasty for patients with chronic thromboembolic pulmonary hypertension are accompanied by increased body mass index and improved nutritional status.

Although balloon pulmonary angioplasty (BPA) improves pulmonary hypertension and the prognosis of patients with chronic thromboembolic pulmonary hypertension (CTEPH), subsequent changes in body mass index (BMI), nutritional status, and appetite have not been fully investigated. This retrospective study aimed to clarify changes in BMI, nutritional status, and appetite after BPA. Fifty-two consecutive patients with CTEPH who underwent complete revascularization with BPA between July 2014 and July 2023 and were available for follow-up were evaluated. We compared the presence or absence of increased appetite, BMI change, and nutritional status before and after BPA treatment. BPA significantly improved the mean pulmonary artery pressure from 37.4 ± 8.7 mmHg to 18.7 ± 2.8 mmHg and the partial pressure of oxygen from 61.6 ± 9.3 mmHg to 82.8 ± 9.9 mmHg (both p < 0.001). Appetite was increased in 82.7% of the patients. BMI significantly increased from 23.9 ± 3.7 kg/m2 to 24.9 ± 3.7 kg/m2 (p < 0.001). As a nutritional indicator, the Geriatric Nutritional Risk Index increased from 105.3 ± 10.2 to 108.3 ± 8.3 (p < 0.001). The median Controlling Nutritional Status scores showed no significant change but the range was significantly improved from 0-9 to 0-3 (p = 0.006). In conclusion, patients with CTEPH show improved oxygenation and hemodynamics, increased BMI, and improved nutritional status following BPA. This sequence of changes may help improve patient prognosis.

Spontaneous hemodynamic improvement after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension is observed within a short term after balloon pulmonary angioplasty.

Natural hemodynamic changes after balloon pulmonary artery angioplasty (BPA) in a unified state without oxygen administration in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains undetermined. This study aimed to clarify the delayed changes in the hemodynamics after BPA in patients with CTEPH. We analyzed 73 consecutive patients with CTEPH who underwent BPA between July 2014 and December 2022. We extracted and evaluated hemodynamic data of the right heart catheter without oxygen administration immediately before and after the first BPA; and immediately before the second BPA, as the "post-delayed changes" after BPA. BPA significantly improved the mean pulmonary artery pressure (mPAP, mmHg) and pulmonary vascular resistance (PVR, dyn-s/cm5) from 36 (32-43) mmHg and 449 (312-627) dyn-s/cm5 before the first BPA to 28 (23-32) mmHg and 275 (217-366) dyn-s/cm5 immediately after BPA, and further significantly improved the values to 23 (20-28) mmHg and 225 (175-301) dyn-s/cm5 post-delayed changes after BPA, respectively. Improvement observed on account of delayed changes was observed both with and without pulmonary hypertension drugs. The delayed changes were observed during a period of 5-180 days, which did not correlate with the changes in mPAP and PVR. Hemodynamic improvement owing to BPA was observed immediately after BPA; however, further improvement was observed as a result of delayed changes. mPAP improved by 3.4 ± 5.2 mmHg and PVR by 53 (10-99) dyn-s/cm5 as delayed improvement. mPAP and PVR showed delayed improved by approximately 10% of their values before BPA.

Inhibitory action of B-type natriuretic peptide on adrenocorticotropic hormone in patients with acute coronary syndrome.

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (ß = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.

Time-dependent changes in P2Y12 reaction unit values for predicting the different types of cardiovascular events in patients with ischemic heart disease.

Several studies have investigated the association between P2Y12 reaction unit (PRU) value and major adverse cardiovascular events (MACEs) in patients with ischemic heart disease, but there is no well-established consensus on the utility of PRU value. Furthermore, the optimal PRU cut-off value varied with studies. One reason may be that the endpoints and observation periods differed, depending on the study. This study aimed to investigate the optimal cut-off and predictive ability of the PRU value for predicting cardiovascular events, while considering different endpoints and observation periods. We surveyed a total of 338 patients receiving P2Y12 inhibitors and measured PRU during cardiac catheterization. Using time-dependent receiver operating characteristic analysis, we evaluated the cut-off and area under curve (AUC) of the PRU value for two MACEs (MACE ①: composite of death, myocardial infarction, stent thrombosis, and cerebral infarction; MACE ②: composite of MACE ① and target vessel revascularization) at 6, 12, 24 and 36 months after cardiac catheterization. MACE ① occurred in 18 cases and MACE ② in 32 cases. The PRU cut-off values at 6, 12, 24, and 36 months were 257, 238, 217, and 216, respectively, for MACE ① and 250, 238, 209, and 204, respectively, for MACE ②. The AUCs at 6, 12, 24, and 36 months were 0.753, 0.832, 0.718, and 0.717, respectively, for MACE ① and 0.724, 0.722, 0.664, and 0.682, respectively, for MACE ②. The optimal cut-off and predictive ability of PRU values for cardiovascular events varied depending on different endpoints and duration of the observation periods. A relatively high PRU value is effective for short-term event suppression, but a low value is required for long-term event suppression.

Effects of angiotensin receptor-neprilysin inhibitor on insulin resistance in patients with heart failure.

AIMS: Although the haemodynamic effects of angiotensin receptor-neprilysin inhibitor (ARNI) on patients with heart failure have been demonstrated, the effect on glucose metabolism has not been fully elucidated. We retrospectively investigated the effect of ARNI on abnormal glucose metabolism in patients with stable chronic heart failure using an additional structural equation model (SEM) analysis. METHODS: We analysed 34 patients who regularly visited to the outpatient department of our institute with heart failure from October 2021 and July 2022 and who were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Seventeen patients switched from ACE inhibitors or ARBs to an ARNI (ARNI group), and the other 17 patients continued treatment with ACE inhibitors or ARBs (control group). RESULTS: At baseline, although the ARNI group included fewer patients with heart failure with preserved ejection fraction in comparison with the control group (P = 0.004), patients with heart failure with mildly reduced ejection fraction, and heart failure with reduced ejection fraction were mostly biased towards the ARNI group (although not statistically significant). The baseline insulin resistance in the ARNI group was already significantly higher in comparison with the control group [fasting blood insulin, 9.7 (7.4, 11.6) vs. 7.8 (5.2, 9.2) µU/mL, P = 0.033; homoeostasis model assessment of insulin resistance (HOMA-IR), 3.10 (1.95, 4.19) vs. 2.02 (1.56, 2.42), P = 0.014]. Three months later, the fasting blood insulin and the HOMA-IR levels were both found to have decreased in comparison with the baseline values [baseline to 3 months: insulin, 9.7 (7.4, 11.6) to 7.3 (4.6, 9.4) µU/mL, P < 0.001; HOMA-IR, 3.10 (1.95, 4.19) to 1.96 (1.23, 3.09), P < 0.001]. An additional SEM analysis demonstrated that the initiation of ARNI had caused a reduction in the fasting blood insulin and the HOMA-IR levels at 3 months independently of the baseline fasting blood insulin and HOMA-IR levels, respectively. Similarly, the initiation of ARNI resulted in a significant reduction in serum uric acid levels (6.28 ± 0.35 to 5.80 ± 0.30 mg/dL, P = 0.008). CONCLUSIONS: In conclusion, even in a short period of only 3 months, the administration of ARNI improved insulin resistance and consequently reduced the serum uric acid levels in patients with stable chronic heart failure. Although the ARNI group already had high insulin resistance at baseline, an additional SEM analysis revealed that the decreased insulin resistance was truly due to the effect of ARNI.

Investigation of the small-balloon technique as a method for retrieving dislodged stents.

The small-balloon technique used to retrieve a dislodged coronary stent is less studied. We investigated the small-balloon technique to study the capture force and retrieval rate of dislodged proximal or distal stents. We developed a retrieval model for stent dislodgement and performed bench tests to compare proximal and distal capture. We evaluated capture force by capture site in a fixed stent dislodgement model and capture force and retrieval rate by capture site using a retrieval model of stent dislodgement. Three-dimensional (3D)-micro-computed tomography (CT) was used to scan the captured conditions of the distal (DC) and proximal (PC) groups. Stent, balloon shaft, and guiding catheter (GC) diameters were measured. Retrieval areas within GC were calculated and compared. The force was significantly lower in the PC group than in the DC group (p < 0.01). Successful retrieval was achieved in 100% and 84.8% in the PC and DC groups, respectively. The force required to retrieve the dislodged stent was significantly lower in the PC group than that in the DC group (p < 0.01). The force was significantly lower in the successful cases in the DC group than in the unsuccessful cases (p < 0.01). The retrievable areas in the PC and DC groups were 67.5% and 32.7%, respectively, as calculated from the values measured from the 3D-CT images. The success rate of PC was higher than that of DC using the small-balloon technique. The smaller proximal stent gap in the PC method facilitated the retrieval of the dislodgement stent.

Sex-inducing effects toward planarians widely present among parasitic flatworms.

Various parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms.

Relationship between haemodynamic indicators and haemogram in patients with heart failure.

AIMS: Pulmonary congestion, reduced cardiac output, neurohumoral factor activation, and decreased renal function associated with decreased cardiac function may have various effects on haemograms. The relationship between these factors and haemograms in patients with heart failure has not been sufficiently investigated. Recently, it was suggested that the lungs are an important site for platelet (Plt) biosynthesis and that it is necessary to study the relationship between pulmonary congestion and Plt count in heart failure in detail. In this study, we examined the relationship between various haemodynamic indicators and haemograms in detail using statistical analyses. METHODS AND RESULTS: A total of 345 patients who underwent cardiac catheterization for the evaluation of cardiac function between 1 January 2015 and 31 December 2020 were included in the study. Haemodynamic indices, including left ventricular end-diastolic pressure (LVEDP) and cardiac index (CI), were measured. Plasma noradrenaline (Nor) concentration, estimated glomerular filtration rate (eGFR), white blood cell (WBC) count, haemoglobin (Hb) level, and Plt count were measured using blood samples collected at the same time. Structural equation modelling (SEM) was used to examine the relationship between LVEDP, CI, plasma Nor concentration, eGFR, WBC count, Hb level, and Plt count. Bayesian inference using SEM was performed for Plt count. A total of 345 patients (mean age: 66.0 ± 13.2 years) were included in this study, and 251 (73%) patients were men. After simple and multiple regression analyses, path diagrams were drawn and analysed using SEM. LVEDP showed a significant negative relationship with Plt count (standardized estimate: -0.129, P = 0.015), and CI showed a significant negative relationship with Hb level (standardized estimate: -0.263, P < 0.001). Plasma Nor concentration showed a significant positive relationship with WBC count (standardized estimate: 0.165, P = 0.003) and Plt count (standardized estimate: 0.198, P < 0.001). The eGFR had a significant positive relationship with Hb level (standardized estimate: 0.274, P < 0.001). Bayesian inference using SEM revealed no relationship between LVEDP and Hb level or WBC count but a significant negative relationship between LVEDP and Plt count. CONCLUSIONS: LVEDP, CI, plasma Nor concentration, and eGFR were related to WBC count, Hb level, and Plt count in patients with heart failure. There was a strong relationship between elevated LVEDP and decreased Plt count, suggesting that pressure overload on the lungs may interfere with the function of the lung as a site of Plt biosynthesis.

[Influence of the Imaging Method on Regional Cerebral Blood Flow Value in Arterial Spin Labeling (ASL): Comparison of Pulsed-ASL with Two-dimensional Acquisition and Pseudo-continuous-ASL with 3D Spiral Acquisition].

PURPOSE: The purposes of this study were to compare regional cerebral blood flow (rCBF) images acquired by the pulsed arterial spin labeling with two-dimensional acquisition (PASL-2D) and the pseudo-continuous-ASL with three-dimensional spiral acquisition (pCASL-3D spiral), and to clarify the characteristics of rCBF values in both ASL methods. METHODS: PASL-2D and pCASL-3D spiral were performed in five healthy volunteers with no history of brain disease using 3T scanners from two venders in the same center. 3D T1-weighted images and rCBF images were acquired by both ASL methods for a total of 3 sessions: twice at the initial visit (1st and 2nd), and 1 hour and 1 week later. The rCBF images calculated by each MR machine were anatomically standardized using SPM12. The regions of interest (ROIs) were set on the territory of the anterior cerebral artery (ACA), the middle cerebral artery (MCA), and the posterior cerebral artery (PCA). Mean and relative rCBF values were calculated at each arterial territory in each session. Reproducibility for rCBF value in each method was analyzed using Bland-Altman plots, the coefficient of repeatability (CR), and the repeatability index (RI). RESULTS: In all sessions, mean values of rCBF were the highest at PCA for PASL-2D and at MCA for pCASL-3D spiral. RIs of pCASL-3D spiral were lower than those of PASL-2D in all arterial territories. CONCLUSION: In the PASL-2D and the pCASL-3D spiral, we confirmed the characteristics of the mean and reproducibility of rCBF values in each arterial territory.

Pulmonary Vein Angioplasty for Pulmonary Vein Stenosis After Ablation Therapy for Atrial Fibrillation　- A Report of 7 Cases.

BACKGROUND: Pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is rare; however, it remains a serious complication. PV angioplasty is reportedly an effective therapy; however, a dedicated device for PV angioplasty has not been developed, and the detailed procedural methods remain undetermined. This study describes the symptoms, indications, treatment strategies, and long-term outcomes for PV stenosis after AF ablation.Methods and Results: This study retrospectively analyzed 7 patients with PV stenosis after catheter ablation for AF and who had undergone PV angioplasty at our hospital during 2015-2021. PV stenosis occurred in the left superior (5 patients) and left inferior (2 patients) PV. Six patients had hemoptysis, chest pain, and dyspnea. Seven de novo lesions were treated using balloon angioplasty (BA) (3 patients), a bare metal stent (BMS) (3 patients), and a drug-coated balloon (DCB) (1 patient). The restenosis rate was 42.9% (n=3; 2 patients in the BA group and 1 patient in the DCB group). The repeat treatment rate was 28.6% (2 patients in the BA group). Stenting was performed as repeat treatment. One patient with subsequent repeat restenosis development underwent BA. Ten PV angioplasties were performed; there were no major complications. CONCLUSIONS: Regarding PV angioplasty after ablation therapy for AF, stenting showed superior long-term PV patency than BA alone; therefore, it should be considered as a standard first-line approach.

The safety and feasibility of retrograde balloon aortic valvuloplasty using the INOUE-BALLOON with severe aortic stenosis.

In the transcatheter aortic valve implantation (TAVI) era, the indications for balloon aortic valvuloplasty (BAV) are increasing. Previously, the INOUE-BALLOON® (IB) was used only for antegrade BAV, but recently, it has also been used for retrograde BAV. However, the safety and feasibility of retrograde BAV using an IB are not fully understood. In this study, we investigated the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe aortic stenosis (AS). We compared 39 cases of retrograde BAV using an IB performed from June 2018 to September 2020 and 34 cases of antegrade BAV using an IB performed from August 2013 to May 2018. The total number of complications was lower in retrograde BAV than in antegrade BAV (p = 0.020). The procedure time was significantly shorter in retrograde BAV than in antegrade BAV (p < 0.001), and the maximum balloon size and number of balloon inflations were smaller in retrograde BAV than in antegrade BAV (p = 0.002 and p < 0.001, respectively). There was no significant difference in the degree of improvement in the aortic valve area or ejection fraction between retrograde and antegrade BAV. In conclusion, the present study showed the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe AS compared with antegrade BAV using an IB.

Heart Failure Treatments Such As Angiotensin Receptor/Neprilysin Inhibitor Improve Heart Failure Status and Glucose Metabolism.

A recent study suggested that angiotensin receptor/neprilysin inhibitor (ARNI; sacubitril/valsartan) can improve functional capacity and cardiac reverse remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Another study suggested that ARNI reduced glycated hemoglobin (HbA1c) in patients with diabetes and HFrEF; however, the details of its efficacy are unknown. We herein report a case of HFrEF with abnormal glucose metabolism in which ARNI was initiated. On the 7th day of admission (before the initiation of ARNI), blood tests showed an abnormal glucose metabolism as follows: fasting blood glucose 134 mg/dL; and fasting blood insulin 11.4 µU/mL (homeostasis model assessment of insulin resistance (HOMA-IR) index 3.77; homeostasis model assessment of ß-cell function (HOMA-ß), 57.8%). On the 23rd day after the initiation of ARNI, even though the patient was not using hypoglycemic drugs, his fasting blood glucose markedly decreased to 70 mg/dL without hypoglycemic symptoms, and his fasting blood insulin decreased to 5.4 µU/mL (HOMA-IR decreased to 0.93, HOMA-ß increased to 277.7%). These results imply that ARNI has the potential to improve insulin resistance and the islet beta-cell function in patients with heart failure, in addition to the original effect of improving the hemodynamics, although the effect of improving the glucose metabolism is also considered to have been influenced by the improvement of the heart failure status and other drugs that the patient was taking.

Redescription of Zeuxapta seriolae (Meserve, 1938) and Zeuxapta australica Lebedev, 1968 (Monogenea: Heteraxinidae).

Redescription is given of heteraxinid monogeneans Zeuxapta seriolae (Meserve, 1938), type species of the genus, and Zeuxapta australica Lebedev, 1968 (formerly Z. seriolae australica). Type specimens of Z. seriolae from Seriola dorsalis from Galápagos Islands were differentiated from Z. australica specimens collected by Lebedev from Seriola glandis (now Seriola lalandi) from Tasman Sea, the type locality, by the shape of the vagina, which consisted of the transversely oval central body and horizontally extended paired tubes in the former, and the transversely oval central body and short, obliquely posteriad paired extensions in the latter. Zeuxapta japonica (Yamaguti, 1940) and Zeuxapta kahala (Yamaguti, 1968) were synonymized with Z. seriolae. Hitherto undescribed Zeuxapta specimens were also examined; those from Seriola aureovittata from Japan and China, and specimens from Seriola dumerili from Japan and Spain were identified as Z. seriolae, while those from Seriola lalandi from Chile and New Zealand were identified as Z. australica. Specimens from S. lalandi (as Seriola glandis) from Heron Island, Australia described by Rohde in 1978 as Z. seriolae consisted of Z. seriolae and Z. australica.

Five new and two known species of Heterobothrium (Monogenea: Diclidophoridae) infecting puffers of the genus Takifugu from Japanese waters.

Seven species of puffers of the genus Takifugu caught in Japanese waters were examined for monogeneans on the gills. Five new species of Heterobothrium (H. gotoi n. sp. from T. porphyreus, H. tabetai n. sp. from T. vermicularis, H. aljufailiae n. sp. and H. iwatai n. sp. from T. snyderi, H. matsubarai n. sp. from T. stictonotus) and two known species (H. praeorchis Bychowsky, Mamaev & Nagibina, 1976 from T. pardalis, T. chrysops and T. flavipterus and H. bychowskyi Ogawa, 1991 from T. flavipterus) were found and described. Heterobothrium tetrodonis of Iwata (1991) was synonymized with H. bychowskyi. Currently, a total of 11 species of Heterobothrium, including the seven species in this study, were recorded from nine species of Japanese Takifugu spp. Ten species excluding H. praeorchis were found from a single host species, suggesting that they are highly host-specific and have co-evolved with the host Takifugu spp. Tagia Sproston, 1946 is synonymized with Heterobothrium. Earlier divergence of Heterobothrium of tetraodontid puffers in Diclidophoridae was suggested by the large subunit ribosomal DNA (rDNA) analyses, and interspecific relationships in this genus inferred from the internal transcribed spacer region of rDNA well corresponded to those inferred from their morphology and adhesive mode to the gills. Including the five new species and synonymization of Tagia with Heterobothrium, the genus Heterobothrium now comprises 19 species.

Impact of Gut Microbiota on the Pharmacokinetics of Glycyrrhizic Acid in Yokukansan, a Kampo Medicine.

Individual differences in gut microbiota can affect the pharmacokinetics of drugs. Yokukansan is a traditional Japanese kampo medicine used to treat peripheral symptoms of dementia and delirium. A study examining the pharmacokinetics of the components of yokukansan reported large individual differences in the pharmacokinetics of glycyrrhizic acid (GL). It is known that GL is metabolized by intestinal bacteria to glycyrrhetinic acid (GA), which is absorbed in the gastrointestinal tract. Thus, the gut microbiota may affect GL pharmacokinetics. We aimed to clarify the relationship between the gut microbiota composition and pharmacokinetics of GL in yokukansan. Mice were orally administered yokukansan, following the administration of various antibiotics, and the plasma concentration of GA and composition of gut microbiota were measured. The GA plasma concentration was low in mice treated with amoxicillin and vancomycin. The composition of gut microbiota revealed a different pattern from that of the control group. Mice with low plasma levels of GA had lower levels of the phylum Bacteroides and Firmicutes. Additionally, bacteria, such as those belonging to the genera Parabaceroides, Bacteroides, Ruminococcus and an unknown genus in families Lachnospiraceae and Ruminococcaceae, exerted positive correlations between the gene copies and plasma GA levels. These bacteria may contribute to the absorption of GA in the gastrointestinal tract, and multiple bacteria may be involved in GL pharmacokinetics. The pharmacokinetics of GL may be predicted by evaluating the composition of gut bacteria, rather than by evaluating the amount of a single bacterium.

Unique crosstalk between platelet and leukocyte counts during treatment for acute coronary syndrome: A retrospective observational study.

In the pathophysiology of acute coronary syndrome (ACS), platelet (PLT) and neutrophil (Neu) crosstalk may be important for activating coagulation and inflammation. It has been speculated that PLTs and Neu may affect each other's cell counts; however, few studies have investigated this hypothesis. In this study, we measured changes in blood cell counts in 245 patients with ACS during treatment and investigated the mutual effects of each blood cell type. Path diagrams were drawn using structural equation modeling, and temporal changes in the count of each blood cell type and the relevance of these changes were analyzed. Throughout the treatment period, the numbers of all blood cell types (red blood cells [RBCs], leukocytes, and PLTs) were associated with each other before and after treatment. A detailed examination of the different cell types revealed that the PLT count at admission had a significant positive effect on the leukocyte (especially Neu) count after treatment. Conversely, the leukocyte (especially Neu) count at admission had a significant positive effect on the PLT count after treatment. During ACS, PLTs and leukocytes, especially Neu, stimulate each other to increase their numbers. The formation of a PLT-leukocyte complex may increase coagulation activity and inflammation, which can lead to a further increase in the counts of both blood cell types.

Emendation of the genus Neoheterobothrium and a proposal of a new genus Paraheterobothrium (Monogenea: Diclidophoridae) for five species of diclidophorids from Pleuronectiform fishes.

Neoheterobothrium chilense González, Oliva & Acuña, 2002 is redescribed based on newly collected specimens from the type host, Hippoglossina macrops and type locality (Coquimbo, Northern Chile). Type specimens of Neoheterobothrium hippoglossini Piasecki, Wierzbicka & Kempter, 2000 and Choricotyle exilis Crane, 1972 are also redescribed. These three diclidophorid monogeneans infecting pleuronectiform flatfishes have pre-ovarian seminal receptacle, ootype inside the semicircle of ovary and elongated pharynx, differentiated from the most similar Orbocotyle Euzet & Suriano, 1975 in that members of the latter genus possess post-ovarian seminal receptacle, post-ovarian ootype and cylindrical or pyriform pharynx. Paraheterobothrium n. g. is proposed for P. chilense n. comb. (type), P. hippoglossini n. comb., P. exilis n. comb., P. papillosum n. comb. and P. syacii n. comb. A redescription of Neoheterobothrium affine (Linton, 1898), the type species of the genus, based on voucher specimens confirmed differences from the new genus in the presence of lamellate plate in the anterior jaw of clamps, absence of seminal receptacle and ovoid pharynx. The genus Neoheterobothrium was emended and N. cynoscioni (MacCallum, 1917) and N. mcdonaldi Payne, 1987 were removed from the genus. Neoheterobothrium now comprises N. affine (type), N. insulare Oliva & Luque, 1995, N. hirame Ogawa, 1999, and N. paralichthyi Suriano & Labriola, 1999, all of them parasites of flatfishes of the genus Paralichthys. Molecular analyses with the internal transcribed spacer 1 distinguished the clade for Paraheterobothrium spp. (P. chilense n. comb. and P. papillosum n. comb.) and Neoheterobothrium spp. (N. hirame, N. affine and N. paralichthyi), supporting this taxonomic emendation.

A pilot cohort study assessing the feasibility of complete revascularization with balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty improves prognosis by alleviating pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension, even with incomplete revascularization. However, hypoxia or the requirement for pulmonary vasodilators often remain even after pulmonary hypertension relief. With this cohort study, we aimed to examine whether complete revascularization by additional balloon pulmonary angioplasty on residual lesions, even after pulmonary hypertension relief, could resolve hypoxia or the requirement for pulmonary vasodilators. During complete revascularization with balloon pulmonary angioplasty in 42 patients with chronic thromboembolic pulmonary hypertension, we investigated therapeutic effects at baseline (T1), pulmonary hypertension relief phase (T2), and at 6 months post-final balloon pulmonary angioplasty (T3). The pulmonary hypertension relief phase was defined as the first time that a mean pulmonary artery pressure ≤ 25 mmHg or pulmonary vascular resistance ≤ 240 dyn-s/cm5 was reached in right heart catheterization before balloon pulmonary angioplasty. The partial pressure of oxygen increased progressively over T1, T2, and T3 (59.2±8.5, 69.0±9.7, and 80.0±9.5 mmHg, respectively; P<0.001 T2 vs. T3). Minimum oxygen saturation levels during the 6-minute walk distance test were 87% (81‒89%), 88% (84‒92%), and 91% (89‒93.3%), respectively (P<0.001 T2 vs. T3), with gradual increase in the 6-minute walk distance (346±125 m, 404±90 m, 454±101 m, respectively; P<0.001 T2 vs. T3). The percentages of patients using pulmonary vasodilators (54.8%, 45.2%, 4.8%, respectively; P<0.001 T2 vs. T3) and requiring oxygen therapy (26%, 26%, 7%, respectively; P = 0.008 T2 vs. T3) decreased significantly without hemodynamic exacerbation or major complications. Despite the discontinuation of pulmonary vasodilators, mean pulmonary artery pressure improved (36.0 [31.0‒41.3], 21.4±4.2, 18.5±3.6 mmHg, respectively; P<0.001 T2 vs. T3). Complete revascularization with balloon pulmonary angioplasty beyond pulmonary hypertension relief benefits patients with chronic thromboembolic pulmonary hypertension; it may improve oxygenation and exercise capacity, and reduce the need for pulmonary vasodilators and oxygen therapy.

A Pilot Evaluation Study of Diffuse Coronary Arterial Contraction Causing Ischemia by Double Measurement of Left Ventriculography Before and After Intracoronary Administration of Nitrates.

Background: Abnormal diffuse coronary artery contraction is not easily diagnosed. In order to evaluate its true risk, we performed double left ventriculography (LVG) before and after intracoronary administration of isosorbide dinitrate (ISDN). We also investigated the relationship between changes in coronary lumen area and changes in left ventricular ejection fraction (LVEF) after ISDN. Methods and Results: The study included 53 patients who underwent an acetylcholine (ACh) provocation test after coronary angiogram and LVG. The second LVG was performed after intracoronary ISDN administration. Coronary lumen area was measured by quantitative coronary arteriography (QCA). Simple and multiple regression analyses showed a significant correlation between changes in total QCA area before and after ISDN administration (pre-and post-total QCA area, respectively) and changes in LVEF. Using structural equation modeling, we observed a negative effect of pre-total QCA area and a positive effect of post-total QCA area on LVEF improvement. Importantly, LVEF improvement was similar between the ACh-positive and -negative groups on the coronary artery spasm test. Receiver operating characteristic curves indicated that the cut-off value at which changes in total QCA area affected changes in LVEF was 5%. Conclusions: Performing double LVG tests before and after ISDN administration may detect myocardial ischemia caused by diffuse coronary artery contraction. The addition of this method to the conventional ACh provocation test may detect the presence of local and/or global myocardial ischemia.