A case of coronary artery compression syndrome resulting from peri-valvular regurgitation and long-standing atrial fibrillation.

A man in his 70s with a history of mitral valve replacement (MVR) and long-standing persistent atrial fibrillation (AF) presented with effort angina. Coronary angiography revealed severe stenosis of the left main coronary artery (LMCA). As it was an emergent case, PCI (percutaneous coronary intervention) was selected for treatment. Intravascular ultrasonography revealed no atherosclerotic lesions in the LMCA. The LMCA was effectively dilated by the drug-eluting stent. No elevation in intracardiac pressure was observed in cardiac catheterization after PCI. Computed tomography scan indicated potential compression of the LMCA by the surrounding structures. In cases of long-standing persistent AF and an enlarged atrium after MVR, the possibility of LMCA stenosis due to anatomical changes should be considered. Learning Objectives: ◾Peri-valvular regurgitation and long-standing persistent atrial fibrillation can potentially cause atrial enlargement.◾Coronary artery stenosis without atherosclerosis can occur due to compression from surrounding structures or shifting of the coronary artery.◾Stent therapy provides a temporary solution and coronary artery bypass grafting or switching should be considered if re-stenosis occurs.

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation.

Background: Symptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce. Objective: We compared the clinical course of SGH occurring with different energy sources. Methods: This multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation. Results: The data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1-4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5-5) days; the total hospitalization duration was 11 [7-19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for >1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set. Conclusions: The clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%.

Signaling pathways upregulating glutathione­specific γ­glutamylcyclotransferase 1 by 3­(5'­hydroxymethyl­2'­furyl)­1­benzylindazole.

Glutathione­specific γ­glutamylcyclotransferase 1 (CHAC1), is an unfolded protein response­induced gene. Although it has been previously reported that CHAC1 transcription is regulated by activating transcription factor (ATF) 4, ATF3 and CCAAT/enhancer­binding protein ß (C/EBPß), the signaling pathways that regulate CHAC1 are largely unknown. It was revealed that 3­(5'­hydroxymethyl­2'­furyl)­1­benzylindazole (YC­1; PubChem ID: 5712), a nitric oxide­independent activator of soluble guanylyl cyclase (sGC), increases CHAC1 levels in cultured human kidney proximal tubular cells (HK­2). Therefore, in the present study, the signaling pathways that induce CHAC1 by YC­1 were investigated in HK­2 cells. YC­1 induced CHAC1 expression in a dose­ and time­dependent manner. KT5823, an inhibitor of cGMP­dependent protein kinase (PKG), partially inhibited CHAC1 upregulation, indicating that the sGC­cGMP­PKG pathway participates in CHAC1 regulation. These results also suggested that other signaling pathways are involved in the regulation of CHAC1. Since antibody array analysis showed the activation of p38, mTOR and Akt, the involvement of these factors was further investigated. Although LY294002 and KU0063794 (inhibitors of Akt and mTOR, respectively) inhibited YC­1­induced CHAC1 expression, SB203580 (an inhibitor of p38) did not. These results indicated that CHAC1 is regulated by the Akt­mTOR pathway. In addition, YC­1 induced endoplasmic reticulum (ER) stress, a regulator of CHAC1 induction. These findings suggested that CHAC1 is regulated by YC­1 through the sGC­cGMP­PKG, Akt­mTOR and ER stress pathways. The present study demonstrated that CHAC1 induction reduced the intracellular glutathione concentration, indicating that CHAC1 plays an important role in intracellular redox homeostasis in tubular cells.

The Attributes of Physicians Assigned to Rural Clinics Designated for Areas without Physicians in Japan.

In Japan, there are rural clinics designated for areas without physicians to ensure the availability of medical care for rural area residents. The purpose of this study was to clarify the attributes of physicians working in the rural clinics. Using the 2018 Ministry of Health, Labour and Welfare data in Japan, we compared the attributes and board certifications of physicians in rural clinics with those of physicians in other clinics. The age group with the highest percentage of physicians was the over 70 group (16%) and the early 30s group (15%) at rural clinics; however, the highest percentage of physicians at other clinics was the 70 over group (20%) and the early 60s group (16%). The number of physicians working in the internal medicine field at rural clinics was 550 (89%). There were 147 (27%) board-certified physicians in that field. Among them, the number of board certifications in internal medicine, surgery, and other than internal medicine or surgery were 79 (54%), 17 (12%), and 51 (35%), respectively. The proportion of board-certified surgery physicians within the internal medicine field in rural clinics was significantly higher than in other clinics (5%). In rural clinics, the age distribution of physicians was different from that in other clinics, and many of the physicians worked in the internal medicine field, but some of them seemed to have a mismatch between their board-certifications and their fields of practice. Further studies are necessary to clarify what the mismatches mean in rural practice.

A case of retractable helix lead auto-retraction: A possible cause of deep septal lead dislodgement.

This paper explains the phenomenon where the helix lead automatically retracts because of residual torque during deep septal pacing.

[Investigation of Improvement Items Based on Students' Perspectives on Practical Training for Raising Pharmaceutical Problem-solving Capability at Pharmacies].

Experience-based clinical training has been introduced in long-term practical training at pharmacies in Japan. Satisfaction and motivation of pharmacy students differs among pharmacies; however, the underlying causes of the differences are unclear. The purpose of this study was to investigate items for improvement for long-term practical training for raising pharmaceutical problem-solving capability at pharmacies based on students' perspectives. We performed a questionnaire survey to evaluate student satisfaction in clinical education and learning environments. The results were analyzed using customer satisfaction (CS) analysis. After long-term practical training at pharmacies, questionnaires were distributed to 126 pharmacy students at Fukuyama University between November 2021 and March 2022. Ninety-eight students responded. "The practice hours per prescription or pharmacotherapy screening and intervention (improvement factor: 14.954)", "the discussion hours for optimization of prescribing and rational medication use, or patient education with pharmacist (9.493)", and "the self-learning place (3.490)" were identified as items requiring improvement. Our findings suggest that the university should work together with pharmacies to improve the learning strategy and environments to increase direct and continuous interaction with pharmacists at pharmacies. Such interventions may result in improvement of students' satisfaction and a wide variety of practical pharmacy skills.

Prevalence of antibodies against human respiratory viruses potentially involving anthropozoonoses in wild bonobos.

One of the current threats to the bonobo (Pan paniscus), a highly endangered ape species only found in the Democratic Republic of the Congo, are anthropozoonoses caused by human respiratory viruses. To date, epidemiological information regarding respiratory viral infections in bonobos is limited. In this study, we examined fecal immunoglobulin A antibodies against human respiratory viruses in bonobos, which may help estimating the viral prevalence. A substantial proportion of bonobos were positive for the antiviral antibodies, including those against parainfluenza virus, respiratory syncytial virus, influenza virus, rhinovirus, and mumps virus. The prevalence of the antibodies was found to depend on the viral species and bonobo populations, suggesting that the bonobos had been exposed to these respiratory viruses. These results may indicate the need for an epidemiological evidence-based action plan for the protection of bonobos from anthropozoonoses.

[Stability of Six Drugs in Total Parenteral Nutrition Solution].

Elneopa NF No. 1 and No. 2 infusions are total parenteral nutrition solutions packaged in four-chambered infusion bags. They have been used as home parenteral nutrition, with various drugs injected into the infusion bags, for treating patient symptoms. In this study, we investigated the stability of six drugs, including famotidine, scopolamine butylbromide, furosemide, bromhexine hydrochloride, betamethasone sodium phosphate, and metoclopramide hydrochloride in the infusion bags under dark conditions at 4℃ for 7 days. Additionally, we developed a high-performance liquid chromatography method to determine drug concentrations in the infusions. The concentrations of injected famotidine, scopolamine butylbromide, and betamethasone sodium phosphate remained unchanged when the four chambers of Elneopa NF No. 1 and No. 2 were opened and the infusions were mixed. Their respective concentrations in the upper and lower chambers also remained unchanged. The concentration of furosemide in the upper chamber of the No. 1 infusion bag decreased after 5 days, although no change was observed in the other chambers and the mixed infusions with the four chambers opened. The concentration of bromhexine hydrochloride slightly decreased in the upper chambers (approximately 3%) after the co-infusion but decreased significantly in the other chambers and the mixed infusions with the four chambers opened. The concentration of metoclopramide hydrochloride significantly decreased in the upper chambers after the co-infusion; however, no change in concentration was observed in the other chambers and the mixed infusion with the four chambers opened. The results of this study provide useful information on home-based parenteral nutrition.

Real-World Safety Profile of Atrial Fibrillation Ablation Using a Second-Generation Cryoballoon in Japan: Insight From a Large Multicenter Observational Study.

OBJECTIVES: This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan. BACKGROUND: Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy. METHODS: This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected. RESULTS: Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia. CONCLUSIONS: This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA.

Efficacy and safety of a combination regimen of phenothrin and ivermectin lotion in patients with head lice in Okinawa, Japan.

In Japan, pyrethroid-resistant head lice have been increasing; however, only 0.4% phenothrin, a pyrethroid drug, is available as an over the counter formulation. In recent years, Sumithrin® Lotion containing 5% phenothrin (PHT) was approved for scabies. In the USA, Sklice® Lotion containing 0.5% ivermectin (IVM) is used for the treatment of pyrethroid-resistant head lice. Therefore, to enhance the treatment of head lice in Japan, we conducted a clinical study to confirm the efficacy and safety of a combination regimen of PHT and IVM (PI regimen). Twelve cases were enrolled and PHT was applied to all patients on day 1. On day 8, five patients (41.7%) were lice free, and PHT was applied again. Notably, seven patients were not lice free and were switched to IVM. The rate of patients who were lice free on the PI regimen, which was the primary end-point, was 75.0% on day 15 and 91.7% on day 22. No adverse events were reported. A genetic analysis of the head lice collected at each visit revealed a kdr mutation in all patients. These results suggest that the PI regimen is safe and effective for the treatment of pyrethroid-resistant head lice in Japan.

[Stability of Insulin in Total Parenteral Nutrition Solutions].

Elneopa NF No. 1 and No. 2 infusions are complete parenteral nutrition solutions packaged as four-chambered bags. They have been used for home parenteral nutrition, with insulin injected into the bags for patients whose blood glucose becomes elevated. In this study, the stability of insulin in No. 1 and No. 2 bags was investigated. The quantity of insulin in Elneopa NF No. 2 was significantly lower than that in Elneopa NF No. 1. When insulin was injected into the upper chamber of either product, decreases in insulin levels were not observed. In contrast, the levels of insulin injected into the lower chamber of both products significantly decreased, with a larger difference in Elneopa NF No. 2. As the amino acid content is different between No. 1 and No. 2, amino acids may be considered a potential cause for the degradation of insulin in the bags. In addition, decreases in insulin levels were observed as the solutions passed through infusion sets just after flushing began, with both Elneopa NF No. 1 and No. 2. In conclusion, the concentration of insulin injected into the Elneopa infusion bags decreases, especially in No. 2 bags, and insulin is absorbed by the infusion sets.

Hypoxia­inducible factor­1α regulates Lipin1 differently in pre­adipocytes and mature adipocytes.

Hypoxia-inducible factor (HIF)-1α is a transcription factor that is activated in low oxygen conditions. Adipose tissues are poorly oxygenated in patients with obesity. The low oxygen conditions in obese adipose tissues induce HIF­1α in adipocytes. Previous studies using genetically modified mice suggest that HIF­1α contributes to dysfunction in adipocytes. Lipin1 is a bifunctional protein that works as a phosphatidate phosphatase and transcriptional coactivator, which regulates lipid metabolism and adipogenesis, respectively. HIF­1α directly regulates Lipin1 in hepatocytes. However, the regulation of Lipin1 by HIF­1α in adipocytes is not well determined. Therefore, the present study investigated the regulation of Lipin1 by HIF­1α in adipocytes. Expression levels of Lipin1 were reduced in epididymal adipose tissues of adipocyte­specific HIF­1α knockout mice, indicating that HIF­1α regulates Lipin1 in adipocytes. In differentiated mature adipocytes, a HIF­1α activator, dimethyloxallyl glycine (DMOG), was demonstrated to increase Lipin1, and a HIF­1α inhibitor, 3­(5'­hydroxymethyl­2'­furyl)-1­benzylindazole (YC­1), reversed this increase, indicating that HIF­1α regulates Lipin1 in differentiated adipocytes. However, during differentiation of pre­adipocytes into adipocytes, YC­1 increased Lipin1 even though HIF­1α was decreased. The differentiation efficiency increased with YC­1 treatment. In addition, DMOG reduced Lipin1 expression levels during differentiation despite increased HIF­1α. Under these conditions, differentiation efficiency was reduced. These results suggest that Lipin1 is negatively regulated by HIF­1α in pre­adipocytes. Our results show that regulation of Lipin1 by HIF­1α is different in adipocytes and pre­adipocytes.

Idiopathic ventricular arrhythmias arising from the posterior septum of tricuspid and mitral annuli: comparison of electrocardiographic characteristics and outcomes of catheter ablation.

PURPOSE: Ventricular arrhythmia (VA) arising from the tricuspid annulus in the posterior septum (PS) (TAPS-VA) has similar electrocardiographic characteristics as VA arising from the mitral annulus in the PS (MAPS-VA) because the two locations are adjacent. We examined the electrocardiographic characteristics that differentiate MAPS-VA from TAPS-VA and the efficacy of catheter ablation. METHODS: We studied 13 patients whose VAs were successfully ablated in the TAPS (n = 7) and MAPS (n = 6). RESULTS: QRS morphologies of both groups were characterized by left and right bundle block morphologies in lead V1, superior axis deviation, and precordial transition at ≤ lead V3 in nine patients. Compared with TAPS-VA, MAPS-VA had (1) R < S wave in lead II, (2) precordial transition in lead V2, (3) s-wave in lead V6, and (4) slurred initial part of the QRS complex in the precordial leads, e.g., [4a] pseudo delta wave ≥ 34 ms, [4b] intrinsicoid deflection time ≥ 85 ms, and [4c] maximum deflection index ≥ 0.55. Patients who met ≥ 2 of (1)-(3) and any of [4a]-[4c] could be classified as having MAPS-VA, with a sensitivity and specificity of 100%. VA recurred in one patient in the TAPS group during the median follow-up of 7 (interquartile range 6 to 15.5) months. CONCLUSIONS: VA arising from the PS has superior axis deviation, and left and right bundle block morphologies with relatively early precordial transition. MAPS-VA can be differentiated from TAPS-VA based on electrocardiographic characteristics. This study provides useful information for treatment involving catheter ablation for VA arising from the PS.

Epidemiological Surveillance of Lymphocryptovirus Infection in Wild Bonobos.

Lymphocryptovirus (LCV) is one of the major gena in the herpesvirus family and is widely disseminated among primates. LCVs of human and rhesus macaques are shown to be causative agents of a number of malignant diseases including lymphoma and carcinoma. Bonobos (Pan paniscus) are highly endangered and the least studied species of the great apes. Considering the potential pathogenicity of the LCV that might threaten the fate of wild bonobos, population-based epidemiological information in terms of LCV prevalence in different location of Bonobo's habitats will help propose improved conservation strategies for the bonobos. However, such data are not available yet because it is very difficult to collect blood samples in the wild and thus virtually impossible to conduct sero-epidemiological study on the wild ape. In order to overcome this issue, we focused on evaluating anti-LCV IgA in the feces of bonobos, which are available in a non-invasive manner. Preliminary study showed that anti-LCV IgA but not IgG was efficiently and reproducibly detected in the feces of captive chimpanzees. It is noteworthy that the fecal IgA-positive individuals were seropositive for both anti-LCV IgG and IgA and that the IgA antibodies in both sera and feces were also detectable by Western blotting assay. These results indicate that the detection of fecal anti-LCV IgA is likely a reliable and feasible for epidemiological surveillance of LCV prevalence in the great apes. We then applied this method and found that 31% of wild bonobos tested were positive for anti-LCV IgA antibody in the feces. Notably, the positivity rates varied extensively among their sampled populations. In conclusion, our results in this study demonstrate that LCV is highly disseminated among wild bonobos while the prevalence is remarkably diverse in their population-dependent manner.

Differences between cardiac memory T wave changes after idiopathic left ventricular tachycardia and ischemic T wave inversion induced by acute coronary syndrome.

BACKGROUND: Cardiac memory (CM) after idiopathic left ventricular tachycardia (ILVT) mimics ischemic T wave inversion (TWI) induced by acute coronary syndrome (ACS). We aimed to establish electrocardiography criteria for differentiating the CM from ischemic TWI. METHODS AND RESULTS: We evaluated 16 ILVT and 48 ACS patients. We identified TWI after ILVT in 9/16 patients (CM group), typically in leads II, III, aVF, aVR, and V4-6. The characteristics of CM were similar to TWI induced by ACS involving right coronary artery, but the CM group had more TWI in V4 and shorter QTc. The criteria of (1) positive T in aVL, (2) negative or isoelectric T in II, and (3) negative T in V4-6 or (4) QTc <430ms were 100% sensitive and 96% specific for the CM group. CONCLUSION: CM after ILVT can be differentiated in most cases from ischemic TWI by the distribution of TWI and the QTc.

Foxc2 in pharyngeal arch mesenchyme is important for aortic arch artery remodelling and ventricular septum formation.

The forkhead box C2 (Foxc2) protein is a member of the forkhead/winged helix transcription factor family and plays an essential role in cardiovascular development. Previous studies showed that Foxc2 null mouse embryos die during midgestation or just after birth with severe cardiovascular defects, including interruption, coarctation of the aortic arch and ventricular septal defects. These are also seen in human congenital heart disease. However, the tissue specific role of Foxc2 in aortic arch remodelling is not yet fully understood. Here we show that Foxc2 is expressed in a restricted pattern in several cell populations, including the mesenchyme and endothelium of pharyngeal arch arteries, which are important for cardiovascular development. In this study, we use a conditional knockout approach to examine the tissue specific role of Foxc2 in aortic arch remodelling. We demonstrate that mouse embryos lacking Foxc2 in Nkx2.5-expressing mesenchyme and endothelium of pharyngeal arch arteries display aortic arch interruption type B and ventricular septal defects. In contrast, conditional deletion of Foxc2 in Tie2-expressing endothelial cells does not result in aortic arch or ventricular septal defects, but does result in embryonic lethality due to peripheral oedema. Our data therefore provide for a detailed understanding of the role of mesenchymal Foxc2 in aortic arch remodelling and in the development of ventricular septum.