Perceptions and Attitudes Toward Telemedicine by Clinicians and Patients in Japan During the COVID-19 Pandemic.

Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. In Japan, the spread of COVID-19 was recognized and a state of emergency declared in April 2020. In response, public health interventions, such as discouraging people from leaving their homes unnecessarily, were enacted across the country. Under these circumstances, telemedicine has received a great deal of social attention, and it has become necessary to identify the perceptions of and attitudes toward telemedicine by clinicians and patients and to clarify the problems and advantages. Materials and Methods: Ten clinicians and 10 family members (if the patient was pediatric or elderly, a caregiver was included) were invited to participate in individual private interviews in 2020. All interviews were conducted from October to December 2020 using a semistructured interview guide. All transcripts were coded using thematic content analysis. Results: Four categories from clinicians and five from patients were identified as perceptions of and attitudes toward telemedicine. Both evaluated the usefulness and convenience of telemedicine in the same manner, but there was a large gap in the content under the safety and problem categories. Discussion: It is necessary to disseminate information about the communication techniques unique to telemedicine to doctors and to improve the "operation and introduction" and "communication environment and device settings" when starting or using telemedicine for all patients. Conclusions: The perceptions and attitudes identified in this study will be useful for establishing and developing a telemedicine system in Japan.

Implications for Social Support on Prolonged Sleep Difficulties among a Disaster-Affected Population: Second Report from a Cross-Sectional Survey in Ishinomaki, Japan.

STUDY OBJECTIVES: This study aimed to investigate the role of social factors, especially social support for sleep, among victims living at home around 1-2 years after the Great East Japan Earthquake and tsunami. DESIGN: A cross-sectional household survey was conducted between May and December 2012 (14-21 months after the disaster) in the Ishinomaki area, Japan. Univariate and multivariate logistic regression models were used to examine the association between social factors, including social support, and prolonged sleep difficulties (persisting over 1 month). Social support was divided into three functions: emotional, informational, and instrumental support. PARTICIPANTS: Data were obtained on 2,593 individuals who were living at home after the disaster. RESULTS: The prevalence of prolonged sleep difficulties was 6.9% (5.8% male, 7.7% female). This study showed that lack of social support has a stronger association with prolonged sleep difficulties than non-modifiable or hardly modifiable consequences caused directly by the disaster, i.e., severity of home damage, change in family structure and income. Among the three dimensions of social support, lack of emotional support showed the strongest association with prolonged sleep difficulties. CONCLUSIONS: Social support, especially emotional support, may positively affect sleep among victims living at home around 1-2 years after a disaster.

Risk of social isolation among Great East Japan Earthquake survivors living in tsunami-affected Ishinomaki, Japan.

OBJECTIVE: The Great East Japan Earthquake and tsunami affected approximately 53 000 people in the city of Ishinomaki, Miyagi Prefecture. Approximately 30 000 people were relocated to temporary/rental housing. The remainder re-inhabited tsunami-affected houses, and their conditions were not known. As social isolation could affect physical and psychological health, we investigated the risk of social isolation among the survivors who returned to their homes. METHODS: The surveyors went door-to-door to the tsunami-affected houses and interviewed each household between October 2011 and March 2012. The participants' risk of social isolation was assessed using 3 factors: whether they have (1) friends to talk with about their problems, (2) close neighbors, and (3) social/family interactions. We analyzed the groups at risk of social isolation and identified the related factors. RESULTS: The elderly (older than age 65 years) were more likely to have close neighbors and social/family interactions, as compared with younger persons. Persons living alone were less likely to have social/family interactions. Non-elderly men who were living alone were the highest proportion of people without social/family interactions. CONCLUSIONS: Our findings suggested that men, particularly those younger than age 65 years and living alone, were at high risk of social isolation and may need attention.

Social ties may play a critical role in mitigating sleep difficulties in disaster-affected communities: a cross-sectional study in the Ishinomaki area, Japan.

STUDY OBJECTIVES: We examined the association between social factors and sleep difficulties among the victims remaining at home in the Ishinomaki area after the Great East Japan Earthquake and Tsunami and identified potentially modifiable factors that may mitigate vulnerability to sleep difficulties during future traumatic events or disasters. DESIGN: A cross-sectional household survey was conducted from October 2011 to March 2012 (6-12 mo after the disaster) in the Ishinomaki area, Japan. Univariate and multivariate logistic regression models were used to examine associations between social factors and sleep difficulties. PARTICIPANTS: We obtained data on 4,176 household members who remained in their homes after the earthquake and tsunami. INTERVENTIONS: N/A. RESULTS: Sleep difficulties were prevalent in 15.0% of the respondents (9.2% male, 20.2% female). Two potentially modifiable factors (lack of pleasure in life and lack of interaction with/visiting neighbors) and three nonmodifiable or hardly modifiable factors (sex, source of income, and number of household members) were associated with sleep difficulties. Nonmodifiable or hardly modifiable consequences caused directly by the disaster (severity of house damage, change in family structure, and change in working status) were not significantly associated with sleep difficulties. CONCLUSIONS: Our data suggest that the lack of pleasure in life and relatively strong networks in the neighborhood, which are potentially modifiable, might have stronger associations with sleep difficulties than do nonmodifiable or hardly modifiable consequences of the disaster (e.g., house damage, change in family structure, and change in work status).

Effect of leucine-to-methionine substitutions on the diffraction quality of histone chaperone SET/TAF-Ibeta/INHAT crystals.

One of the most frequent problems in crystallization is poor quality of the crystals. In order to overcome this obstacle several methods have been utilized, including amino-acid substitutions of the target protein. Here, an example is presented of crystal-quality improvement by leucine-to-methionine substitutions. A variant protein with three amino-acid substitutions enabled improvement of the crystal quality of the histone chaperone SET/TAF-Ibeta/INHAT when combined with optimization of the cryoconditions. This procedure improved the resolution of the SET/TAF-Ibeta/INHAT crystals from around 5.5 to 2.3 A without changing the crystallization conditions.

Relationship between the structure of SET/TAF-Ibeta/INHAT and its histone chaperone activity.

Histone chaperones assemble and disassemble nucleosomes in an ATP-independent manner and thus regulate the most fundamental step in the alteration of chromatin structure. The molecular mechanisms underlying histone chaperone activity remain unclear. To gain insights into these mechanisms, we solved the crystal structure of the functional domain of SET/TAF-Ibeta/INHAT at a resolution of 2.3 A. We found that SET/TAF-Ibeta/INHAT formed a dimer that assumed a "headphone"-like structure. Each subunit of the SET/TAF-Ibeta/INHAT dimer consisted of an N terminus, a backbone helix, and an "earmuff" domain. It resembles the structure of the related protein NAP-1. Comparison of the crystal structures of SET/TAF-Ibeta/INHAT and NAP-1 revealed that the two proteins were folded similarly except for an inserted helix. However, their backbone helices were shaped differently, and the relative dispositions of the backbone helix and the earmuff domain between the two proteins differed by approximately 40 degrees . Our biochemical analyses of mutants revealed that the region of SET/TAF-Ibeta/INHAT that is engaged in histone chaperone activity is the bottom surface of the earmuff domain, because this surface bound both core histones and double-stranded DNA. This overlap or closeness of the activity surface and the binding surfaces suggests that the specific association among SET/TAF-Ibeta/INHAT, core histones, and double-stranded DNA is requisite for histone chaperone activity. These findings provide insights into the possible mechanisms by which histone chaperones assemble and disassemble nucleosome structures.

Functional interaction between the transcription factor Krüppel-like factor 5 and poly(ADP-ribose) polymerase-1 in cardiovascular apoptosis.

Krüppel-like factor 5 (KLF5) is a transcription factor important in regulation of the cardiovascular response to external stress. KLF5 regulates pathological cell growth, and its acetylation is important for this effect. Its mechanisms of action, however, are still unclear. Analysis in KLF5-deficient mice showed that KLF5 confers apoptotic resistance in vascular lesions. Mechanistic analysis further showed that it specifically interacts with poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme important in DNA repair and apoptosis. KLF5 interacted with a proteolytic fragment of PARP-1, and acetylation of KLF5 under apoptotic conditions increased their affinity. Moreover, KLF5 wild-type (but not a non-acetylatable point mutant) inhibited apoptosis as induced by the PARP-1 fragment. Collectively, we have found that KLF5 regulates apoptosis and targets PARP-1, and further, for acetylation to regulate these effects. Our findings thus implicate functional interaction between the transcription factor KLF5 and PARP-1 in cardiovascular apoptosis.

Simple histone acetylation plays a complex role in the regulation of gene expression.

Eukaryotic DNA is packaged into chromatin by histone proteins, which assemble the DNA into an organized, higher-order structure. The precise organization of chromatin is essential for faithful execution of DNA-mediated reactions such as transcription, DNA replication, DNA repair and DNA recombination. The organization of chromatin is considered to be regulated by a variety of post-translational modifications of histones, such as acetylation, methylation, phosphorylation, ubiquitination, SUMOylation and poly-ADP-ribosylation. The relationship between histone acetylation and gene expression was first observed in 1964. Since then, a great deal of evidence has accumulated showing that not only transcription but other DNA-mediated reactions also are regulated by histone acetylation. With regard to the putative mechanism(s) by which histone acetylation regulates the flow of genetic information, site-specific modification and recognition of acetylated histone/DNA complexes have been postulated. Elucidation of the downstream effects of histone modification, as well as the identification, isolation and characterization of the relevant factors involved, have aided in our understanding of the mechanisms of regulation of DNA activity by histones. Currently, state-of-the-art technologies that enable genome-wide analysis are allowing insight into a critical and interesting question in eukaryotic transcription: are the principles that govern transcription of individual gene loci applicable to the genome as a whole? Here, we review the recent progress on histone modifications, with an emphasis on the role of histone acetylation in gene expression.

The deacetylase HDAC1 negatively regulates the cardiovascular transcription factor Krüppel-like factor 5 through direct interaction.

Transcription is regulated by a network of transcription factors and related cofactors that act in concert with the general transcription machinery. Elucidating their underlying interactions is important for understanding the mechanisms regulating transcription. Recently, we have shown that Krüppel-like factor KLF5, a member of the Sp/KLF family of zinc finger factors and a key regulator of cardiovascular remodeling, is regulated positively by the acetylase p300 and negatively by the oncogenic regulator SET through coupled interaction and regulation of acetylation. Here, we have shown that the deacetylase HDAC1 can negatively regulate KLF5 through direct interaction. KLF5 interacts with HDAC1 in the cell and in vitro. Gel shift DNA binding assay showed that their interaction inhibits the DNA binding activity of KLF5, suggesting a property of HDAC1 to directly affect the DNA binding affinity of a transcription factor. Reporter assay also revealed that HDAC1 suppresses KLF5-dependent promoter activation. Additionally, overexpression of HDAC1 suppressed KLF5-dependent activation of its endogenous downstream gene, platelet-derived growth factor-A chain gene, when activated by phorbol ester. Further, HDAC1 binds to the first zinc finger of KLF5, which is the same region where p300 interacts with KLF5 and, intriguingly, HDAC1 inhibits binding of p300 to KLF5. Direct competitive interaction between acetylase and deacetylase has been hitherto unknown. Collectively, the transcription factor KLF5 is negatively regulated by the deacetylase HDAC1 through direct effects on its activities (DNA binding activity, promoter activation) and further through inhibition of interaction with p300. These findings suggest a novel role and mechanism for regulation of transcription by deacetylase.

[Edema in heart disease].

The two main causes of cardiac edema are congestive heart failure and pericardial diseases. Careful evaluation of patients with edema is important because there are many other diseases showing the symptom. Important for the treatment of edema is to restrict sodium and water intake. Diuretics and digoxin have formed the mainstay of treatment for many years. Patients with edema should be given diuretics until an euvolemic state is achieved. Especially loop diuretic is effective to reduce edema quickly. Recently atrial natriuretic peptide and brain natriuretic peptide are shown to be useful markers to assess heart failure. These peptides are also useful as therapeutic tools for treating edema in heart failure. Even if the patient has responded favorably to diuretics, angiotensin converting enzymes inhibitors, angiotensin II receptor blockers, beta blockers and spironolactone should be added according to the status, because there are many evidences that they improve the long-term prognosis. Vasopeptidase inhibitors and vasopressin antagonist are being introduced for management of heart failure.

Purification, crystallization and preliminary X-ray analysis of Methanococcus jannaschii TATA box-binding protein (TBP).

TATA box-binding protein (TBP) from Methanococcus jannaschii has been crystallized by the hanging-drop vapour-diffusion method using PEG MME 2000 as a precipitant. The crystal belongs to space group P21, with unit-cell parameters a = 53.2, b = 55.5, c = 123.4 A,a = 90.0, fi = 91.0, y = 90.0 degrees, and contains four molecules in the asymmetric unit. A data set was collected to 1.9 A resolution using synchrotron radiation. A molecular-replacement solution was found using the structure of TBP from Sulfolobus acidocaldarius as a model. Crystallographic refinement is in progress.

Purification, crystallization and preliminary X-ray diffraction analysis of human oncoprotein SET/TAF-1beta.

The human oncoprotein SET/TAF-1beta has been crystallized by the sitting-drop vapour-diffusion method using ammonium sulfate as a precipitant. The crystal belongs to space group C2, with unit-cell parameters a = 119.6, b = 62.8, c = 61.0 A, beta = 89.7 degrees, and contains two molecules in the asymmetric unit. A complete data set was collected to 2.8 A resolution using synchrotron radiation.

Positive and negative regulation of the cardiovascular transcription factor KLF5 by p300 and the oncogenic regulator SET through interaction and acetylation on the DNA-binding domain.

Here we show a novel pathway of transcriptional regulation of a DNA-binding transcription factor by coupled interaction and modification (e.g., acetylation) through the DNA-binding domain (DBD). The oncogenic regulator SET was isolated by affinity purification of factors interacting with the DBD of the cardiovascular transcription factor KLF5. SET negatively regulated KLF5 DNA binding, transactivation, and cell-proliferative activities. Down-regulation of the negative regulator SET was seen in response to KLF5-mediated gene activation. The coactivator/acetylase p300, on the other hand, interacted with and acetylated KLF5 DBD, and activated its transcription. Interestingly, SET inhibited KLF5 acetylation, and a nonacetylated mutant of KLF5 showed reduced transcriptional activation and cell growth complementary to the actions of SET. These findings suggest a new pathway for regulation of a DNA-binding transcription factor on the DBD through interaction and coupled acetylation by two opposing regulatory factors of a coactivator/acetylase and a negative cofactor harboring activity to inhibit acetylation.

Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.

Transcription involves molecular interactions between general and regulatory transcription factors with further regulation by protein-protein interactions (e.g. transcriptional cofactors). Here we describe functional interaction between DNA-binding transcription factor and histone chaperone. Affinity purification of factors interacting with the DNA-binding domain of the transcription factor Sp1 showed Sp1 to interact with the histone chaperone TAF-I, both alpha and beta isoforms. This interaction was specific as Sp1 did not interact with another histone chaperone CIA nor did other tested DNA-binding regulatory factors (MyoD, NFkappaB, p53) interact with TAF-I. Interaction of Sp1 and TAF-I occurs both in vitro and in vivo. Interaction with TAF-I results in inhibition of DNA-binding, and also likely as a result of such, inhibition of promoter activation by Sp1. Collectively, we describe interaction between DNA-binding transcription factor and histone chaperone which results in negative regulation of the former. This novel regulatory interaction advances our understanding of the mechanisms of eukaryotic transcription through DNA-binding regulatory transcription factors by protein-protein interactions, and also shows the DNA-binding domain to mediate important regulatory interactions.