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Aims Fibrosis‐4 index (FIB‐4 index), calculated by age, aspartate aminotransferase, alanine aminotransferase, and platelet count, is a simple marker to evaluate liver fibrosis and is associated with right‐sided heart failure. However, the clinical relevance of FIB‐4 in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. We investigated the prognostic implication of the FIB‐4 index regarding right ventricular dysfunction in patients with HFpEF. Methods and results This prospective study included 116 consecutive HFpEF patients (mean age 79 years, 43% male) hospitalized with acute decompensated heart failure. We evaluated the association of the FIB‐4 index with right ventricular function determined by tricuspid annular plane systolic excursion (TAPSE) and tricuspid lateral annular systolic velocity (S′) before discharge. Cox regression analysis was performed to evaluate the association between the FIB‐4 index and major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, readmission for heart failure, nonfatal myocardial infarction, and nonfatal stroke. FIB‐4 index before discharge was significantly lower than that at admission (2.62 [1.92–3.46] and 3.03 [2.05–4.67], median [interquartile range], P

Among the elder abuse cases reported to Matsudo City, Chiba Prefecture (population 487,091 as of April 1, 2017) from fiscal year (FY) 2017 to FY 2019. Of the 525 reported cases, 497 for which records could be judged to be accurate were included in the study. There were 119 cases (23.9%) in which the abusers were presumed to have a disability. Out of these 119 cases, the abusers of 86 (72.3%) cases were not involved with health and welfare policies for people with disabilities or such involvement had been suspended. If the abuser had received support in the field of health and welfare for the disabled or as a person in need at an early stage, the elder abuse might not have occurred. Support for people with disabilities and support for persons in financial need are required before they become abusers.

The Elder Abuse Prevention Law mainly defines “elder abuse” inflicted by caregivers. Elder abuse by non-caregivers is therefore rarely covered by the law. We investigated domestic elder abuse reported in Matsudo City, Chiba, Japan, to determine the number of domestic elder abuse cases excluded from legal protection but constituting elder abuse defined by WHO. From April 2017 to March 2020, the municipal elder protection services agency received 525 reports of domestic elder abuse. We studied the effective records of 497 of these cases. 299 cases were confirmed elder abuse cases defined by the law, with 198 excluded. However, 176 out of the 198 excluded cases constitute elder abuse defined by WHO. In these 176 cases, abuse was perpetrated by non-caregivers. Due to the current formation of the law, this abuse went undetected and unprotected. We think amendment of the law is required to protect these excluded cases.

Long noncoding RNAs (lncRNAs) are vastly transcribed and extensively studied but lncRNAs overlapping with the sense orientation of mRNA have been poorly studied. We analyzed the lncRNA DAPALR overlapping with the 5´ UTR of the Doublesex1 (Dsx1), the male determining gene in Daphnia magna. By affinity purification, we identified an RNA binding protein, Shep as a DAPALR binding protein. Shep also binds to Dsx1 5´ UTR by recognizing the overlapping sequence and suppresses translation of the mRNA. In vitro and in vivo analyses indicated that DAPALR increased Dsx1 translation efficiency by sequestration of Shep. This regulation was impaired when the Shep binding site in DAPALR was deleted. These results suggest that Shep suppresses the unintentional translation of Dsx1 by setting a threshold; and when the sense lncRNA DAPALR is expressed, DAPALR cancels the suppression caused by Shep. This mechanism may be important to show dimorphic gene expressions such as sex determination and it may account for the binary expression in various developmental processes., Author summary Long noncoding RNAs are vastly transcribed throughout the genome. Among them, RNAs overlapping the protein-coding RNA in sense orientation have been poorly studied because of the difficulty in differentiating their sequences from their overlapping coding RNAs although this class of RNAs has been reported to comprise the majority of the long noncoding RNAs. In the crustacean Daphnia magna, a long noncoding RNA, called DAPALR, is transcribed from the male determining gene, Doublesex1, and overlaps with the Doublesex1 5´ UTR. DAPALR activates Doublesex1 but this regulatory mechanism remains unknown. We found the RNA binding protein Shep bound to the Doublesex1 5´ UTR. In vitro and in vivo experiments indicated that Shep suppresses translation of the mRNA and DAPALR increases Doublesex1 translation efficiency by sequestration of Shep. Since male-specific expression of Doublesex1 is also regulated at the transcriptional level, we propose that Shep cancels the unexpected expression of Doublesex1 and maintains the feminized state for sexual dimorphism but DAPALR suppresses this repression by sequestration of Shep. We infer that this mechanism is not only for binary sex regulation but could function in the binary regulation of other genes in various biological processes.

The COVID-19 became a pandemic in early 2020. It was found, at first, that the main manifestations of this new virus occur through respiratory and constitutional symptoms. Therefore, chest tomography was elected as the best imaging test to assess the extent of pulmonary involvement and as a good prognostic predictor for the disease. However, as new studies were produced, the gastrointestinal involvement of COVID-19 becomes more evident, with reports from patients who manifested mainly or only gastrointestinal symptoms in the course of the disease. Thus, in some cases, the initial investigation is carried out at the emergency department with an abdominal computed tomography. We report a case series of ten patients who came to the emergency department of our institution with a chief gastrointestinal complaint, and were initially submitted to an abdominal computed tomography as the first investigation. Although most of the patients did not have significant changes in the abdominal images, most reported patients had pulmonary findings visualized at the lung bases, which were later designated as typical COVID-19 pulmonary findings on chest computed tomography. Only one patient had atypical COVID-19 lung changes on chest computed tomography. All patients had a positive real-time polymerase chain reaction for COVID-19. It is imperative to alert radiologists, especially abdominal radiologists, with the possibility of COVID-19 isolated gastrointestinal symptoms. Besides, it must become a habit to radiologists to assess the pulmonary basis on abdominal scans, a site commonly affected by the new coronavirus.

The disease caused by the new coronavirus, or COVID-19, has been recently described and became a health issue worldwide. Its diagnosis of certainty is given by polymerase chain reaction. High-resolution computed tomography, however, is useful in the current context of pandemic, especially for the most severe cases, in assessing disease extent, possible differential diagnoses and searching complications. In patients with suspected clinical symptoms and typical imaging findings, in which there is still no laboratory test result, or polymerase chain reaction is not available, the role of this test is still discussed. In addition, it is important to note that part of the patients present false-negative laboratory tests, especially in initial cases, which can delay isolation, favoring the spread of the disease. Thus, knowledge about the COVID-19 and its imaging manifestations is extremely relevant for all physicians involved in the patient care, clinicians or radiologists. RESUMO A doença causada pelo novo coronavírus, ou COVID-19, foi descrita recentemente e tornou-se uma questão de saúde mundial. Seu diagnóstico de certeza é dado pela reação em cadeia da polimerase. A tomografia computadorizada de alta resolução, entretanto, mostra-se útil no contexto atual de pandemia, especialmente nos casos mais graves, na avaliação da extensão da doença, em possíveis diagnósticos diferenciais e na pesquisa de complicações. Em pacientes com quadro clínico suspeito e achados de imagem típicos, nos quais ainda não há resultado laboratorial ou a reação em cadeia da polimerase não se encontra disponível, ainda se discute o papel desse exame. Importante ressaltar que parte dos pacientes apresenta exames laboratoriais falsos-negativos, notadamente em casos iniciais, o que pode retardar medidas de isolamento, favorecendo a propagação da doença. Dessa forma, o conhecimento da COVID-19 e de suas manifestações nos exames de imagem é de extrema importância para os médicos envolvidos no atendimento, sejam clínicos ou radiologistas.

Objectives The current study was performed to determine whether pulmonary vein isolation (PVI) improves nocturnal hypertension in patients with paroxysmal atrial fibrillation (PAF). Background Abnormal night-time blood pressure (BP) fluctuation is a risk factor for atrial fibrillation. Imbalance of autonomic nervous function is a risk factor common to both of these abnormalities. PVI can reportedly modify the autonomic nervous function balance in patients with atrial fibrillation. Methods The study population comprised 50 consecutive patients (mean age, 69.8 ± 7.5 years; 35.0% male) with PAF scheduled for PVI. Both 24-h ambulatory BP monitoring and heart rate variability analysis were performed before and at 3 months after PVI. Results Patients were classified into two groups according to the presence of nocturnal BP dipping before PVI: the normal dipping group (n = 27) and the nondipping group (n = 23). The low-frequency spectrum power and the ratio of low-frequency spectrum power to high-frequency spectrum power (low-frequency spectrum/high-frequency spectrum) were higher in the nondipping than the normal dipping group (low-frequency spectrum: 219.9 ± 210.2 vs. 92.7 ± 50.5 ms, respectively, P = 0.03; low-frequency spectrum/high-frequency spectrum: 1.8 ± 1.9 vs. 0.9 ± 0.8, respectively, P = 0.05). In the nondipping group, the elevated night-time BP disappeared in eight (35%) patients at 3 months after PVI, which was associated with an increase in high-frequency spectrum power. These patients did not develop atrial fibrillation recurrence during follow-up (mean, 568 ± 218 days). Conclusion Among patients with PAF, the nondipping group showed greater sympathetic activity (higher low-frequency spectrum power and low-frequency spectrum/high-frequency spectrum) than the dipping group. Restoration of BP dipping after PVI is associated with increased parasympathetic activity (higher high-frequency spectrum power) and reduced recurrence of arrhythmic events.

Ground-glass opacity is a very frequent and unspecified finding in chest computed tomography. Therefore, it admits a wide range of differential diagnoses in the acute context, from viral pneumonias such as influenza virus, coronavirus disease 2019 and cytomegalovirus and even non-infectious lesions, such as vaping, pulmonary infarction, alveolar hemorrhage and pulmonary edema. For this diagnostic differentiation, ground glass must be correlated with other findings in imaging tests, with laboratory tests and with the patients’ clinical condition. In the context of a pandemic, it is extremely important to remember the other pathologies with similar findings to coronavirus disease 2019 in the imaging exams. RESUMO A opacidade em vidro fosco é uma alteração muito frequente e pouco específica na tomografia computadorizada de tórax. Ela admite grande leque de diagnósticos diferenciais no contexto agudo, desde pneumonias virais, como as causadas pelo vírus influenza, pela doença do coronavírus 2019 e pelo citomegalovírus, até mesmo lesões de origem não infecciosa, como vaping , infarto pulmonar, hemorragia alveolar e edema pulmonar. Para essa diferenciação diagnóstica, deve-se correlacionar o vidro fosco com os demais achados nos exames de imagem, exames laboratoriais e quadro clínico do paciente. É de suma importância, no contexto de pandemia, recordar as demais patologias com os achados semelhantes aos da doença do coronavírus 2019 nos exames de imagem.

The disease caused by the new coronavirus, or COVID-19, has been recently described and became a health issue worldwide. Its diagnosis of certainty is given by polymerase chain reaction. High-resolution computed tomography, however, is useful in the current context of pandemic, especially for the most severe cases, in assessing disease extent, possible differential diagnoses and searching complications. In patients with suspected clinical symptoms and typical imaging findings, in which there is still no laboratory test result, or polymerase chain reaction is not available, the role of this test is still discussed. In addition, it is important to note that part of the patients present false-negative laboratory tests, especially in initial cases, which can delay isolation, favoring the spread of the disease. Thus, knowledge about the COVID-19 and its imaging manifestations is extremely relevant for all physicians involved in the patient care, clinicians or radiologists.

The COVID-19 became a pandemic in early 2020. It was found, at first, that the main manifestations of this new virus occur through respiratory and constitutional symptoms. Therefore, chest tomography was elected as the best imaging test to assess the extent of pulmonary involvement and as a good prognostic predictor for the disease. However, as new studies were produced, the gastrointestinal involvement of COVID-19 becomes more evident, with reports from patients who manifested mainly or only gastrointestinal symptoms in the course of the disease. Thus, in some cases, the initial investigation is carried out at the emergency department with an abdominal computed tomography. We report a case series of ten patients who came to the emergency department of our institution with a chief gastrointestinal complaint, and were initially submitted to an abdominal computed tomography as the first investigation. Although most of the patients did not have significant changes in the abdominal images, most reported patients had pulmonary findings visualized at the lung bases, which were later designated as typical COVID-19 pulmonary findings on chest computed tomography. Only one patient had atypical COVID-19 lung changes on chest computed tomography. All patients had a positive real-time polymerase chain reaction for COVID-19. It is imperative to alert radiologists, especially abdominal radiologists, with the possibility of COVID-19 isolated gastrointestinal symptoms. Besides, it must become a habit to radiologists to assess the pulmonary basis on abdominal scans, a site commonly affected by the new coronavirus.

Background In Brugada syndrome (BrS), it has been reported that delayed activation in the RV is related to the development of type-1 ECG which is more critical than type-2. On the other hand, the coexistence of complete right bundle-branch block (CRBBB), which also causes delayed activation in the RV, sometimes makes typical BrS ECG misleading. We hypothesized that premature stimulation of the RV can unmask the influence of delayed activation in the RV and convert the morphology of ECG in BrS patients. Methods and results In 35 BrS patients with type-1 ECG including 8 patients with concomitant CRBBB and 6 control subjects with CRBBB, progressively premature single stimulations were delivered from the RV apex on electrophysiological study. Then we evaluated QRS morphology of fusion beats created by single premature stimulation in each patient. In 29 (83%) of 35 the BrS patients, conversion from type-1 to type-2 ECG was observed during the process of single premature stimulation. Additionally, in all 8 BrS patients with concomitant CRBBB, type-1 or type-2 BrS ECG was revealed by premature stimulation with relief of CRBBB. These findings were not observed in any of the control subjects with CRBBB. Conclusion Single premature stimulation of the RV converts ECG from type-1 to type-2 in most BrS cases and unmasks type-1 ECG in all BrS cases with CRBBB. Our results could suggest that type-1 ECG is associated with delayed activation of the RV compared with type-2 ECG. This article is protected by copyright. All rights reserved

ObjectiveAlthough blood pressure (BP) is a major determinant of arterial stiffness, whether high pulse wave velocity (PWV) adversely influences cardiac parameters and cardiovascular (CV) outcome in patients without high BP remains unclear.MethodsOutpatients without high BP (n=320), defined as systolic BP ≥140 mm Hg, were enrolled in this retrospective study. At baseline, all patients underwent echocardiography and multidetector CT to determine the coronary artery calcification (CAC) score. Arterial stiffness was assessed based on brachial-ankle PWV (baPWV), from which patients were classified into two groups: those with high (≥18 m/s, n=89) and low baPWV (ResultsIn multivariable linear regression analysis, baPWV was significantly associated with CAC score and serum N-terminal pro-brain natriuretic peptide hormone level, after adjustment for confounding factors. In multivariable logistic regression analysis, baPWV ≥18 m/s was significantly associated with CAC score ≥400 (OR 2.466, 95% CI 1.012 to 6.009, p=0.0471). Kaplan-Meier analysis showed that the high-baPWV group experienced more CV events during the 575 days of follow-up (20% vs 6%, p=0.0003).ConclusionsHigh baPWV was associated with greater CAC and a high risk of a future CV event, especially coronary artery disease, even in patients without high BP.

Objective Multi-slice computed tomography (MSCT) coronary angiography has been reported as an effective alternative to invasive conventional coronary angiography (CCA) for the diagnosis of coronary artery disease (CAD). However, in previous reports, the diagnostic accuracy of MSCT has not been significant enough to be of benefit in symptomatic patients. The aim of this study was to identify the usefulness of 320-slice computed tomography coronary angiography (320-CTA) for symptomatic patients in terms of the diagnostic accuracy of 320-CTA and the prevalence of vasospastic angina pectoris (VSAP) within the study cohort. Methods We retrospectively analyzed 513 consecutive symptomatic patients with suspected CAD who had undergone 320-CTA and CCA. We determined the diagnostic accuracy of 320-CTA using CCA as the reference standard. Ergonovine provocation tests were performed on patients without significant coronary artery stenosis on CCA. Results Of the total cohort of 513 symptomatic patients, 39% had obstructive CAD. The patient based analysis of the accuracy of 320-CTA showed a sensitivity of 91.0%, a specificity of 71.0%, a positive predictive value of 66.5%, and a negative predictive value of 92.5%. Of the 314 symptomatic patients who did not have significant coronary artery stenosis on CCA, 58 (18%) were diagnosed with VSAP using ergonovine provocation tests. Discussion The negative and positive predictive values indicate that 320-CTA cannot replace CCA for symptomatic patients. Indeed, a combination of CCA and ergonovine provocation tests should be taken into consideration for symptomatic patients.

A 76-year-old man taking theophylline was admitted to our hospital with congestive heart failure and supraventricular tachycardia (SVT). After admission, he developed cardiogenic shock as a result of SVT storm, which was refractory to medical treatment including adenosine and electrical cardioversion. The serum theophylline concentration at admission was identified as toxic. Therefore, theophylline toxicity was considered as a major cause of the SVT storm. Hemodynamic stability was achieved by using mechanical circulatory support. Additionally, continuous hemodiafiltration was performed to remove theophylline, and it was effective for suppression of SVT. The patient was successfully weaned off mechanical circulatory support. After the patient's general status had improved, an electrophysiological study was performed, and it showed orthodromic atrioventricular reentrant tachycardia with a right free wall accessory pathway. Radiofrequency catheter ablation was successfully performed. .

Matsudo City is preparing to implement an ordinance so that 3 protective services for children, older persons, and people with disabilities can work together for efficient prevention. Supporting pregnant women is sometimes effective for prevention of future child abuse. Supporting people with disabilities is often prevention of future neglect caused by them. Supporting perpetrators and victims of domestic violence is effective to prevent future elder abuse by interruption of abusive behaviors. We expect to prevent abuses by affiliation of various protective and supportive services. According to the Elder Abuse Prevention Law, elder abuse is defined as those inflicted by caregivers. Therefore, there is a big problem that abuses by non-caregivers are excluded from the coverage of the law. We are currently investigating abuses by non-caregivers to clarify the proportion of excluded cases among those reported to Elder Protective Services. I would like to talk about preliminary result of our investigation.

Nuclear factor κB (NFκB), which is composed of the RelA and p50 subunits, binds to NFκB response elements (NREs) and stimulates the transcription of inflammation-related genes. Here, locked nucleic acid (LNA) antisense oligonucleotides (ASOs) complementary to the termini of the 3'- and 5'-untranslated regions (UTRs) of the RelA mRNA were generated; these molecules were named 3'-LNA and 5'-LNA, respectively. To evaluate their effects on NFκB activity, HeLa cells were co-transfected with the LNA ASOs and a luciferase reporter gene carrying an NRE. Transfection of the cells with 3'-LNA reduced NFκB activity by 30-40%, without affecting RelA mRNA accumulation. Concomitant transfection of HeLa cells with 5'-LNA and 3'-LNA resulted in a 70% reduction in NFκB activity. Furthermore, partial poly(A) tail shortening occurred in LNA ASO-transfected cells. We also employed triethylene glycol as a spacer to link 5'-LNA and 3'-LNA. Reporter gene assays showed that the spacer-linked LNA ASO reduced NFκB activity similarly to a combination of 5'-LNA and 3'-LNA. In addition, an in vitro translation assay revealed that spacer-linked LNA ASOs inhibited the translation of a target mRNA in a specific manner. In summary, this study describes a novel antisense method capturing the target mRNA at independent positions.

Background Recent clinical trials have demonstrated the efficacy of short-term treatment with tolvaptan, an oral vasopressin V2 receptor antagonist, in patients with heart failure. However, the response to tolvaptan varies among patients. The aim of this study was to determine factors associated with response to tolvaptan in patients with acute decompensated heart failure (ADHF). Methods The Tolvaptan Registry, a prospective, observational, multicenter cohort study performed in Japan, aims to determine factors affecting the responsiveness of tolvaptan in patients with ADHF. We enrolled ADHF patients treated with tolvaptan and they were divided into two groups: responders and non-responders. Responders were defined as subjects who met all of the following three conditions: (1) increasing urine volume during a 24-hour period after the start of tolvaptan treatment; (2) improvement in New York Heart Association functional class; and (3) decrease in cardiothoracic ratio assessed by chest X-ray on day 3 of tolvaptan administration. Results Among the 114 patients, treatment with tolvaptan improved three conditions of heart failure in more than half of all the cohorts (71 patients, 62%). As for baseline characteristics, estimated glomerular filtration rate, urine osmolality, and kidney size were significantly greater in responders than in non-responders. Multivariate logistic analysis revealed that kidney size was independently associated with responders (odds ratio: 1.083, p = 0.001, 95% confidence interval 1.031–1.137). Conclusions The main clinical characteristic of responders to treatment with tolvaptan is that kidney size is preserved.

Drug development involves pharmacometric experiments in animals. Such experiments should limit animal pain and stress. Conventional murine models of atopic dermatitis (AD) used in drug development are generated by weekly painting of hapten on dorsal skin for 5 weeks. The present study aimed to develop a protocol that involves less animal distress. The experiments focused on serum total IgE levels, which are a marker of AD. The conventional protocol induced ever rising IgE levels. Experiments with extended intervals between sensitizations showed that IgE peaked ~5 days after the second sensitization, after which it returned to the control level within 12–19 days. An additional third sensitization on day 28 further increased the serum IgE level. In the 4–5 days after the second sensitization, the dorsal skin exhibited typical AD-like lesions with edema, scabs, epithelial-cell hypertrophy, marked mast-cell and lymphocyte infiltration of dermis, and increased IL-4, IL-6, IL-10, IL-1β, IL-17A, IFN-γ and TNF-α expression. Thus, two 2,4-dinitrofluorobenzene sensitizations yield a murine AD model in less than 20 days. This study shows that animal model protocols used in drug development can be fine-tuned so that they remain effective yet cause animals less stress and pain.