The Role of Long Non-Coding RNAs in Cardiovascular Diseases.

Long non-coding RNAs (lncRNAs) are non-coding RNA molecules longer than 200 nucleotides that regulate gene expression at the transcriptional, post-transcriptional, and translational levels. Abnormal expression of lncRNAs has been identified in many human diseases. Future improvements in diagnostic, prognostic, and therapeutic techniques will be facilitated by a deeper understanding of disease etiology. Cardiovascular diseases (CVDs) are the main cause of death globally. Cardiac development involves lncRNAs, and their abnormalities are linked to many CVDs. This review examines the relationship and function of lncRNA in a variety of CVDs, including atherosclerosis, myocardial infarction, myocardial hypertrophy, and heart failure. Therein, the potential utilization of lncRNAs in clinical diagnostic, prognostic, and therapeutic applications will also be discussed.

Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality.

BACKGROUND: The COVID-19 pandemic increased the use of broad-spectrum antibiotics due to diagnostic uncertainty, particularly in critical care. Multi-professional communication became more difficult, weakening stewardship activities. AIM: To determine changes in bacterial co-/secondary infections and antibiotics used in COVID-19 patients in critical care, and mortality rates, between the first and second waves. METHODS: Prospective audit comparing bacterial co-/secondary infections and their treatment during the first two waves of the pandemic in a single-centre teaching hospital intensive care unit. Data on demographics, daily antibiotic use, clinical outcomes, and culture results in patients diagnosed with COVID-19 infection were collected over 11 months. FINDINGS: From March 9th, 2020 to September 2nd, 2020 (Wave 1), there were 156 patients and between September 3rd, 2020 and February 1st, 2021 (Wave 2) there were 235 patients with COVID-19 infection admitted to intensive care. No significant difference was seen in mortality or positive blood culture rates between the two waves. The proportion of patients receiving antimicrobial therapy (93.0% vs 81.7%; P < 0.01) and the duration of meropenem use (median (interquartile range): 5 (2-7) vs 3 (2-5) days; P = 0.01) was lower in Wave 2. However, the number of patients with respiratory isolates of Pseudomonas aeruginosa (4/156 vs 21/235; P < 0.01) and bacteraemia from a respiratory source (3/156 vs 20/235; P < 0.01) increased in Wave 2, associated with an outbreak of infection. There was no significant difference between waves with respect to isolation of other pathogens. CONCLUSION: Reduced broad-spectrum antimicrobial use in the second wave of COVID-19 compared with the first wave was not associated with significant change in mortality.

Validation of the Chinese version of joint protection self-efficacy scale in patients with rheumatoid arthritis.

OBJECTIVE: To develop and validate the Chinese version of the Joint Protection Self-Efficacy Scale (CJP-SES) in patients with rheumatoid arthritis (RA) in China. METHOD: (1) Translation of the original German/English version JP-SES and cultural adaptation into the Chinese language; (2)Validation of the CJP-SES with the Chinese versions of the Arthritis Self-Efficacy Scale-8 (ASES-8), the Laffrey Health Conception Scale (LHCS), 10-item Perceived Efficacy in Patient-Physician Interactions Scale (PEPPI-10), Disease Activity Score-28 (DAS-28) and Health Assessment Questionnaire (HAQ). Instrument measurement included reliability testing, item generation, construct validity, test-retest reliability, and correlation with other measurements. Confirmatory factor analysis was applied to determine construct validity and internal consistency. One hundred fifteen patients with RA were investigated. RESULT: Finally, 105 RA patients were included in the analysis. Confirmatory factor analysis demonstrated fit for a unidimensional model of the JP-SES. Additionally, the scale showed internal consistency (Cronbach's α coefficient 0.922), kappa coefficient (0.653), and test-retest reliability (ICC = 0.94). Weak correlations with other scores for the other instruments, such as the Chinese version of ASES-8 (0.263) and PEPPI-10 (0.326). Correlation with duration (0.274), moderate correlation with BMI (- 0.438) and DAS-28 (- 0.493), and strong correlation with HAQ (- 0.644) were found in this research. CONCLUSION: This is the first study to adapt and validate the JP-SES into Chinese for use in patients with RA. Our research showing that the CJP-SES has a good construct validity, internal consistency, and test-retest reliability. This scale can help doctors and nurses to assess the self-efficacy of patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: TJYY-YLS-036.

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators.

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks.

The effect of a forced-air warming blanket on patients' end-tidal and transcutaneous carbon dioxide partial pressures during eye surgery under local anaesthesia: a single-blind, randomised controlled trial.

Surgical drapes used during eye surgery are impermeable to air and hence risk trapping air underneath them. We investigated the effect of a forced-air warming blanket on carbon dioxide accumulation under the drapes in patients undergoing eye surgery under local anaesthesia without sedation. Forty patients of ASA physical status 1 and 2 were randomly assigned to either the forced-air warmer (n = 20) or a control heated overblanket (n = 20). All patients were given 1 l.min(-1) oxygen. We measured transcutaneous and end-tidal carbon dioxide partial pressures, heart rate, arterial pressure, respiratory rate, temperature and oxygen saturation before and after draping, then every 5 min thereafter for 30 min. The mean (SD) transcutaneous carbon dioxide partial pressure in the forced-air warming group stayed constant after draping at 5.7 (0.2) kPa but rose to a maximum of 6.4 (0.4) kPa in the heated overblanket group (p = 0.0001 for the difference at time points 15 min and later). We conclude that forced-air warming reduces carbon dioxide accumulation under the drapes in patients undergoing eye surgery under local anaesthesia.

Mitochondrial protein turnover: methods to measure turnover rates on a large scale.

Mitochondrial proteins carry out diverse cellular functions including ATP synthesis, ion homeostasis, cell death signaling, and fatty acid metabolism and biogenesis. Compromised mitochondrial quality control is implicated in various human disorders including cardiac diseases. Recently it has emerged that mitochondrial protein turnover can serve as an informative cellular parameter to characterize mitochondrial quality and uncover disease mechanisms. The turnover rate of a mitochondrial protein reflects its homeostasis and dynamics under the quality control systems acting on mitochondria at a particular cell state. This review article summarizes some recent advances and outstanding challenges for measuring the turnover rates of mitochondrial proteins in health and disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".

Healing under pressure: hyperbaric oxygen and myocutaneous flap repair for extreme persistent perineal sinus after proctectomy for inflammatory bowel disease.

AIM: Persistent perineal sinus (PPS) following proctectomy for inflammatory bowel disease affects about 50% of patients. Up to 33% of cases of PPS remain unhealed at 12 months and the most refractory cases are unhealed at 24 months despite optimal conventional therapy. Reports of hyperbaric oxygen therapy (HBOT) for chronic wounds and Crohn's perianal disease led us to explore perioperative HBOT with rectus abdominis myocutaneous (RAM) flap repair in a highly selected group of patients with extreme PPS who had failed all other interventions. METHOD: Patients with extreme PPS received preoperative HBOT (a 90-min session at 2.2-2.4 atmospheres, five times per week for 5-6 weeks, for a total of up to 30 sessions), before abdominoperineal PPS excision and perineal reconstruction with vertical or transverse RAM flap repair within 2-4 weeks of completing HBOT. Postoperative HBOT (10 further 90-min sessions) was administered within 2 weeks where practicable. RESULTS: Between 2007 and 2011, four patients with extreme PPS underwent RAM flap repair with preoperative HBOT; two also received postoperative HBOT. The median (range) duration of PPS before HBOT was 88.5 (23-156) months. All patients had previously failed multiple (5 to > 35) surgical procedures. Complete healing occurred in all patients at a median (range) follow-up of 2.5 (2-3) months. There were no further hospital admissions for PPS at a median (range) follow-up of 35 (8-64) months. CONCLUSION: Hyperbaric oxygen therapy combined with PPS excision and perineal reconstruction with a RAM flap led to complete perineal healing in four patients with extreme PPS and appears a safe and effective extension to the therapeutic pathway for exceptionally treatment-refractory PPS.

Identification of secreted proteins during skeletal muscle development.

The differentiation program of skeletal muscle cells is exquisitely sensitive to secreted proteins. We developed a strategy to maximize the discovery of secreted proteins, using mass spectrometry-based proteomics, from cultured muscle cells, C2C12, grown in a serum-free medium. This strategy led to the identification of 80 nonredundant proteins, of which 27 were secretory proteins that were identified with a minimum of two tryptic peptides. A number of the identified secretory proteins are involved in extracellular matrix remodeling, cellular proliferation, migration, and signaling. A putative network of proteins involving matrix metalloproteinase 2, SPARC, and cystatin C that all interact with TGFbeta signaling has been postulated to contribute toward a functional role in the myogenic differentiation program.

Synthesis and evaluation of novel aldose reductase inhibitors: Effects on lens protein kinase Cgamma.

PURPOSE: To synthesize novel aldose reductase inhibitors (ARI) that will normalize losses in protein kinase Cgamma (PKCgamma) observed during diabetes and galactosemia. METHODS: ARI were synthesized as tricyclic pyrones 1-6 (HAR-1 through HAR-6) from 3-methyl-1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran and (5aS,7S)-7-isopropenyl-3-methyl-1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran and were tested by inhibition of aldose reductase enzyme activity in vitro and by inhibition of polyol formation in lens epithelial cells in culture. Identified compounds were further tested in galactosemic rat lens in vivo for (a) normalized PKCgamma levels by Western blot, (b) reduction of phosphorylation of the gap junction protein Cx46 by analyses of co-immunoprecipitated proteins, and (c) by normalization of gap junction activity as measured by dye transfer. RESULTS: HAR-1 (1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran-3-acetic acid) was identified as an ARI with IC50 for aldose reductase inhibition at 2 nM. Polyol accumulation in lens epithelial cells was reduced by 80% at 10 microM. Rats fed 40% galactose for 9 days had an 80% reduction in PKCgamma levels which were normalized by HAR-1 at 100 mg/kg/day, fed orally. Phosphorylation of Cx46 was increased by 50% and this was normalized in HAR-1 treated rats (6 day treatment). Gap junction activity of galactosemic rats was reduced by 55% and this was normalized by HAR-1 in six day-treated rats. CONCLUSIONS: HAR-1 is a novel ARI which normalized losses of PKCgamma, changes in Cx46 phosphorylation, and gap junction activity.

Nasopharyngeal carcinoma complicated by pseudohypertrophic osteoarthropathy.

This paper describes a case of nasopharyngeal carcinoma complicated by pseudohypertrophic osteoarthropathy due to pulmonary metastasis following radiotherapy. A similar clinical picture may be seen in pseudohypertrophic osteoarthropathy, rheumatoid arthritis and carcinomatous arthritis. It is important clinically to differentiate them from one another. One should search carefully for an intrathoracic secondary lesion when pseudohypertrophic osteoarthropathy occurs in a case of nasopharyngeal carcinoma following radiotherapy.