The role of long noncoding RNA (lncRNA) in adult hearts is unknown; also unclear is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes undergo antisense transcription, ...including myosin heavy chain 7 (Myh7), which encodes molecular motor proteins for heart contraction. Here we identify a cluster of lncRNA transcripts from Myh7 loci and demonstrate a new lncRNA-chromatin mechanism for heart failure. In mice, these transcripts, which we named myosin heavy-chain-associated RNA transcripts (Myheart, or Mhrt), are cardiac-specific and abundant in adult hearts. Pathological stress activates the Brg1-Hdac-Parp chromatin repressor complex to inhibit Mhrt transcription in the heart. Such stress-induced Mhrt repression is essential for cardiomyopathy to develop: restoring Mhrt to the pre-stress level protects the heart from hypertrophy and failure. Mhrt antagonizes the function of Brg1, a chromatin-remodelling factor that is activated by stress to trigger aberrant gene expression and cardiac myopathy. Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus inhibiting chromatin targeting and gene regulation by Brg1. It does so by binding to the helicase domain of Brg1, a domain that is crucial for tethering Brg1 to chromatinized DNA targets. Brg1 helicase has dual nucleic-acid-binding specificities: it is capable of binding lncRNA (Mhrt) and chromatinized--but not naked--DNA. This dual-binding feature of helicase enables a competitive inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets to prevent chromatin remodelling. A Mhrt-Brg1 feedback circuit is thus crucial for heart function. Human MHRT also originates from MYH7 loci and is repressed in various types of myopathic hearts, suggesting a conserved lncRNA mechanism in human cardiomyopathy. Our studies identify a cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodelling factors, and establish a new paradigm for lncRNA-chromatin interaction.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Healthcare-associated infections caused by multidrug-resistant (MDR) pathogens are significantly associated with increased mortality and morbidity. Environmental cleaning can reduce transmission of ...these pathogens but is often inadequate. Adjunctive methods are warranted to enhance the effectiveness of disinfection particularly in hospital settings where healthcare-associated infections are of major concern.
We conducted a study to examine the effectiveness of a mobile, automatic device, Hyper Light Disinfection Robot (model: Hyper Light P3), which utilized ultraviolet-C (UV-C) to kill MDR-Pseudomonas aeruginosa, MDR- Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Mycobacterium abscessus and Aspergillus fumigatus. The performance of this device in disinfecting hospital rooms previously admitted by patients harboring MRSA and VRE was also assessed.
Except for VRE and M. abscessus, more than 3 log10 reduction of vegetative bacteria colonies was observed after UV-C irradiation of 5 min at a distance of 3 m from the device. At the distance of 1 m, substantial and comparable reduction of colonies was observed across all tested microorganisms regardless of exposure time. The killing effect was less pronounced for A. fumigatus particularly at the distance of 2–3 m. In uncleaned hospital rooms, there was significant reduction in the number of bacteria colonies sampled from different surfaces after UV-C irradiation for 15 min.
UV-C disinfection system was effective in killing MDR pathogens. Further study is warranted to confirm its effectiveness as an adjunctive method in disinfecting hospital environment.
Nosocomial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a growing threat due to the limited therapeutic choices and high mortality rate. The aim of this study was to ...evaluate the prognostic factors for mortality in patients with nosocomial pneumonia caused by CRGNB and the impact of colistin-based therapy on the outcomes of intensive care unit (ICU) patients. We conducted a retrospective study of the ICUs in five tertiary teaching hospitals in Taiwan. Patients with nosocomial pneumonia caused by CRGNB from January 2016 to December 2016 were included. Prognostic factors for mortality were analyzed using multivariate logistic regression. The influence of colistin-based therapy on mortality and clinical and microbiological outcomes were evaluated in subgroups using different severity stratification criteria. A total of 690 patients were enrolled in the study, with an in-hospital mortality of 46.1%. The most common CRGNB pathogens were Acinetobacter baumannii (78.7%) and Pseudomonas aeruginosa (13.0%). Significant predictors (odds ratio and 95% confidence interval) of mortality from multivariate analysis were a length of hospital stay (LOS) prior to pneumonia of longer than 9 days (2.18, 1.53-3.10), a sequential organ failure assessment (SOFA) score of more than 7 (2.36, 1.65-3.37), supportive care with vasopressor therapy (3.21, 2.26-4.56), and escalation of antimicrobial therapy (0.71, 0.50-0.99). There were no significant differences between the colistin-based therapy in the deceased and survival groups (42.1% vs. 42.7%, p = 0.873). In the subgroup analysis, patients with multiple organ involvement (> 2 organs) or higher SOFA score (> 7) receiving colistin-based therapy had better survival outcomes. Prolonged LOS prior to pneumonia onset, high SOFA score, vasopressor requirement, and timely escalation of antimicrobial therapy were predictors for mortality in critically ill patients with nosocomial CRGNB pneumonia. Colistin-based therapy was associated with better survival outcomes in subgroups of patients with a SOFA score of more than 7 and multiple organ involvement.
Abstract
Background
The prevalence of HIV and hepatitis B virus (HBV) co‐infection is higher in Asia than in Europe and North America and varies significantly between different regions within Asia. ...Important routes of transmission of both these infections include high‐risk unprotected sexual contact, intravenous drug use, and transmission of maternal infection perinatally or in early childhood. While life expectancy among people living with HIV has been extended with effective antiretroviral therapy (ART), HBV‐induced liver injury and complications have emerged as a leading cause of morbidity and mortality in people living with HIV.
Objectives
This article describes the prevalence of co‐infection, current clinical practice, and recommendations for the management of people living with HIV‐HBV co‐infection in Asia.
Results and Conclusions
Screening for HBV should occur at the time of HIV diagnosis; however, HBV screening rates in people living with HIV in Asia vary widely by region. Similarly, people with HBV should be screened for HIV before initiation of HBV antiviral therapy. People with HIV‐HBV co‐infection should be assessed for liver damage and risk factors for liver disease and be monitored regularly for liver complications and HBV DNA. Medical treatment with ART is lifelong and includes tenofovir and lamivudine or emtricitabine, unless intolerant or contraindicated, as these are active against both HIV and HBV. HBV vaccination programmes are effective in reducing co‐infection rates. Mother‐to‐child transmission can be prevented through measures such as vaccination, antenatal screening, and treatment of pregnant women who are infected.
Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo. Capsule ...locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn't. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer (P < 0.001), a higher percentage had pneumonia (P = 0.004), and the white blood cell count was lower (P = 0.03). Infection with KL2 A. baumannii predicted mortality (adjusted hazard ratio aHR, 2.03; 95% confidence interval CI, 1.09-3.78; P = 0.03), independently of the Pitt bacteraemia score (aHR, 1.34; 95% CI, 1.23-1.46; P < 0.001) and leucopenia (aHR, 2.16; 95% CI, 1.30-3.57; P = 0.003). Thrombocytopenia contributed to the effect of KL2 on mortality in bacteraemia (Sobel test P = 0.01). Large-scale studies are warranted to confirm these findings and the underlying mechanisms deserve further investigation.
Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net ...production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy.
Aims
This study examined the changes and the predictors of suicide ideation/suicide attempt and the moderating effects of psychosocial factors on the suicide ideation/suicide attempts among human ...immunodeficiency virus (HIV)‐positive patients at 6–12 months post‐diagnosis.
Background
Suicide behaviours are prevalent among newly diagnosed HIV‐positive patients, but the changes in suicide behaviours after diagnosis and the role of psychosocial factors in these behaviours are not well studied.
Design
This study used a prospective longitudinal design.
Methods
A total of 113 participants diagnosed as HIV‐positive for 6–12 months were recruited from the outpatient department. Data were collected from June 2015 – October 2016. They were asked to complete Beck's Scale for Suicide Ideation, the Beck Depression Inventory‐II, the Body Image Scale, the Meaning in Life Questionnaire and the Multidimensional Scale of Perceived Social Support at baseline, the third month and the sixth month.
Results
The results showed the high occurrence rates for suicide ideation ranging from 27.2%, 21.6%, and 25.8% and suicide attempt ranging from 14.7%, 8.6%, and 13.3% at the baseline, the third month and the sixth month, respectively. The education level, social support from family and depressive symptoms were the predictors of suicide ideation. The history of depression disorders, depressive symptoms and social support from friends significantly predicted suicide attempt. Meaning in life‐presence moderated the relationship between depressive symptoms and suicide ideation.
Conclusions
After diagnosed for 6–12 months, HIV‐positive patients remain the high‐risk group for suicide ideation and attempt. Suicide intervention targeting the risk and protective factors are required for HIV‐positive patients.
目的
研究HIV阳性患者确诊后6‐12个月自杀意念/自杀企图的变化与预测因素,以及心理社会因素对自杀意念/自杀企图的调节作用。
背景
自杀行为在新确诊的HIV阳性患者中非常普遍,但诊断后自杀行为的变化及心理社会因素在这些行为中的作用尚未得到很好的研究。
设计
本研究采用前瞻性纵向设计。
方法
共从门诊部招募了113名参与者,他们在6‐12个月内被确诊为HIV阳性。收集2015年6月—2016年10月间的数据。要求参与者在基线期、第3个月和第6个月填写Beck自杀意念量表、Beck抑郁问卷II、体象量表、生活意义问卷及多维领悟社会支持量表。
结果
研究结果表明,在基线期、第3个月和第6个月,自杀意念的高发率分别为27.2%、21.6%和25.8%;自杀企图的高发率分别为14.7%、8.6%和3.3%。自杀意念的预测因素为教育水平、来自家庭的社会支持及抑郁症状。抑郁症史、抑郁症状、和来自朋友的社会支持明显预测了自杀企图。生活意义缓和了抑郁症状和自杀意念之间的关系。
结论
HIV阳性患者在确诊6‐12个月后,仍是自杀意念和自杀企图的高危人群。HIV阳性患者需要针对风险和保护因素的自杀干预。
In an era advocating cradle-to-cradle designs, resource recycling should involve not only waste sorting but also remanufacturing practices to produce products made of recycled wastes. However, ...consumers nowadays no longer demand products that are only visually appealing. Therefore, adding different sensory elements to product designs has emerged as a new design approach. With a focus on applying designs for all five senses to recycled merchandise, this study investigated the level of importance consumers attach to the types and five sensory applications of recycled merchandise and subsequently analyzed the factors involved to identify the possibility of developing recycled merchandise. Regarding research methods, literature analysis was performed to collate information relevant to recycled merchandise and designs for all five senses. Expert interview method was employed to gather expert opinions across different disciplines. Questionnaire survey was used to further understand how consumers perceive products that are remanufactured using design elements for all five senses. The study results revealed that (1) most consumers held a positive attitude toward design of recycled products using five senses; (2) more communication channels can be created between recycled merchandise and consumers; (3) consumers preferred recycled merchandise of pragmatic value and paid closer attention to the sensory element of touch; and (4) recycled merchandise can be made more sophisticated and less vulgar to draw the attention of consumers. After consumer preference for recycled merchandise is determined, this information can serve as a reference for selling these products in a way that propels consumers to spread positive word-of-mouth and be more willing to purchase recycled merchandise.
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality ...in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.
To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia.
...This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed.
In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37–0.92; model 2: aOR 0.37, 95% CI 0.21–0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2.
Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.
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