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Bioorganic & Medicinal Chemistry Dec 2023Bromodomain and PHD finger-containing (BRPF) proteins function as epigenetic readers that specifically recognize acetylated lysine residues on histone tails. The...
Bromodomain and PHD finger-containing (BRPF) proteins function as epigenetic readers that specifically recognize acetylated lysine residues on histone tails. The acetyl-lysine binding pocket of BRPF has emerged as an attractive target for the development of protein interaction inhibitors owing to its potential druggability. In this study, we identified 3-acetylindoles as bone antiresorptive agents with a novel scaffold by performing structure-based virtual screening and hit optimization. Among those derivatives, compound 18 exhibited potent and selective inhibitory activities against BRPF1B (IC = 102 nM) as well as outstanding inhibitory activity against osteoclastogenesis (73.8% @ 1 μM) and differentiation (IC = 0.19 μM) without cytotoxicity. Besides, cellular mechanism assays demonstrated that compound 18 exhibited a strong bone antiresorptive effect by modulating the RANKL/RANK/NFATc1 pathway. Structural and functional studies on BRPF1 inhibitors aid in making advances to understand the epigenetic mechanisms of bone cell development and create innovative therapeutics for treating bone metastases from solid tumors and other bone erosive diseases.
Topics: Osteogenesis; Osteoclasts; NF-kappa B; Receptor Activator of Nuclear Factor-kappa B; Bone Density Conservation Agents; Ligands; Lysine; Cell Differentiation; RANK Ligand; NFATC Transcription Factors
PubMed: 37951134
DOI: 10.1016/j.bmc.2023.117440 -
HeartRhythm Case Reports Nov 2023
PubMed: 38023679
DOI: 10.1016/j.hrcr.2023.08.010 -
BMC Oral Health Apr 2024Mouth dryness increases the risk of some oral health-related conditions. Furthermore, it is unclear if patients with dry mouth engage in appropriate oral health-related...
BACKGROUND
Mouth dryness increases the risk of some oral health-related conditions. Furthermore, it is unclear if patients with dry mouth engage in appropriate oral health-related behaviours. The study examined oral health, related behaviours, and perceived stress in dry-mouth patients and compared them to matched controls without mouth dryness.
METHODS
Information about 182 dry-mouth patients and 302 age- and sex-matched subjects was retrieved. Three dry mouth groups: xerostomia, Sicca syndrome and Sjögren's syndrome, were formed based on patient self-reported and objectively assessed symptoms. The World Health Organization's Oral Health for Adults and Perceived Stress Scale (PSS-10) questionnaires inquired about sociodemographic characteristics, oral health-related behaviours, and self-perceived stress. Clinical oral health assessments included: caries experience measured as total numbers of decayed (DS), missing (MS), filled surfaces (FS), number of remaining teeth, erosive tooth wear and extent of periodontal pocketing. Data were analyzed using bivariate and multivariable tests.
RESULTS
The dry-mouth participants had higher mean (SD) DMFS scores than their matched controls: xerostomia patients vs. controls: 74.6 (34.4) and 66.3 (35.4), Sicca syndrome patients vs. controls: 88.3 (34.0) and 70.1 (33.9), and Sjögren's syndrome patients vs. controls: 95.7 (31.5) and 74 (33.2). In comparison to controls, individuals with Sicca and patients with Sjögren's syndromes had lower mean (SD) number of remaining teeth, 15.9 (10.1) vs. 21.7 (8.4) and 13.8 (10.0) vs. 20.1 (9.2), and a lower mean (SD) extent of periodontal pocketing, 20.7 (28.6) vs. 41.1 (31.0), and 21.2 (24.1) vs. 34.8 (34.2), respectively. Xerostomia, Sicca syndrome and Sjögren's syndrome patients had higher odds of using fluoridated toothpaste; OR 1.8 (95%CI 1.1-2.9), OR 5.6 (95%CI 1.7-18.3) and OR 6.9 (95%CI 2.2-21.3), respectively. Participants with Sjögren's syndrome had lower odds of the last dental visit being within the last year; OR 0.2 (95%CI 0.1-0.8).
CONCLUSIONS
Dry-mouth patients had higher caries experience and fewer teeth than comparison groups but a lower extent of periodontal pocketing. Even though more participants with dry mouth used fluoridated toothpastes, their oral health-related behaviours were not optimal.
Topics: Adult; Humans; Sjogren's Syndrome; Oral Health; Cross-Sectional Studies; Xerostomia; Periodontal Pocket; Dental Caries; Stress, Psychological; Psychological Tests; Self Report
PubMed: 38622697
DOI: 10.1186/s12903-024-04224-7 -
Journal of Cardiovascular... Apr 2024The implantation of a cardiac implantable electronic device (CIED) can have esthetic and psychological consequences on patients. We explore a heart team model for care...
INTRODUCTION
The implantation of a cardiac implantable electronic device (CIED) can have esthetic and psychological consequences on patients. We explore a heart team model for care coordination and discuss esthetic approaches for improved cosmetic outcomes in patients undergoing (CIED)-related procedures or de novo implantation.
METHODS
Patients undergoing CIED surgery for approved indications between June 2015 and June 2022 were identified. Patients were included when surgical care was provided by a collaborative relationship between the primary electrophysiologist and the plastic surgeon. Patient demographics, details of the surgical procedure, information on breast implants, complications, and outcomes related to cosmesis were recorded.
RESULTS
Twenty-two female patients were included in this study. The mean age was 50.2 ± 18.2 years. The mean follow-up duration was 2.2 ± 5.5 months. The top two indications for the procedure included CIED generator change (n = 9, 41%) and implantable cardioverter-defibrillator (ICD) implantation (n = 7, 32%). The most common reasons for involving plastic surgery in the procedure included surgery near breast implants (n = 10, 45%) and device displacement or discomfort (n = 8, 36%). CIED pocket position was prepectoral in 10 cases (45%), subpectoral in 11 patients (50%), and intramuscular in one patient (4.5%). The majority of the patients (20, 91%) had cosmetically acceptable results postprocedure. One patient (4.5%) had breast asymmetry on the CIED side, and another continued to have skin erosion over the CIED and leads.
CONCLUSION
A heart team approach incorporating the expertize of cardiac electrophysiology and plastic surgery is essential for providing optimal care for patients with breast implants and patients requesting esthetic appeal.
Topics: Humans; Female; Adult; Middle Aged; Aged; Pacemaker, Artificial; Defibrillators, Implantable; Breast Implants; Cardiac Surgical Procedures; Retrospective Studies
PubMed: 38361241
DOI: 10.1111/jce.16196 -
Arquivos Brasileiros de Cirurgia... 2024Bariatric surgery can cause oral health problems in individuals, such as an increase in dental caries, periodontal diseases and dental erosion, which can be avoided if... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bariatric surgery can cause oral health problems in individuals, such as an increase in dental caries, periodontal diseases and dental erosion, which can be avoided if oral health promotion actions are implemented.
AIMS
To assess the impact of an oral health promotion program implemented among gastroplasty patients.
METHODS
This randomized clinical trial involved 208 patients undergoing gastroplasty; they were divided into two groups: Intervention Group, with participation in the Oral Health Promotion Program for Bariatric Patients, or Control Group. Assessments were carried out preoperatively, and six and 12 months postoperatively. The oral conditions assessed were: dental caries, periodontal diseases, tooth wear, dental plaque, and salivary flow. Sociodemographic information was obtained through application of structured questionnaires. For data analysis, the Chi-Square, Fisher's Exact, and Mann-Whitney tests were performed - α=5%.
RESULTS
Patients in the Intervention Group, when compared to those in the Control Group, presented: fewer changes in enamel (6M: p<0.0001; 12M: p=0.001), in dentin (6M: p<0.0001; 12M: p<0.0001), moderate tooth wear (6M=0.002; 12M=0.005), gingival bleeding (6M: p<0.0001), dental calculus (6M=0.002; 12M: p=0.03), periodontal pocket 4-5 mm (6M=0.001; 12M: p=<0.0001); greater reduction in the bacterial plaque index (6M: p<0.0001; 12M: p<0.0001), and increased salivary flow (6M: p=0.019).
CONCLUSIONS
The oral health promotion program had a positive impact on the prevention and control of the main problems to the oral health of the gastroplasty patients.
Topics: Humans; Male; Oral Health; Female; Gastroplasty; Middle Aged; Adult; Health Promotion
PubMed: 38896700
DOI: 10.1590/0102-6720202400011e1804 -
Spinal Cord Series and Cases Nov 2023Intrathecal baclofen (ITB) therapy is an effective method of treating spasticity in persons with spasticity due to spinal cord injury (SCI), but complications are not...
INTRODUCTION
Intrathecal baclofen (ITB) therapy is an effective method of treating spasticity in persons with spasticity due to spinal cord injury (SCI), but complications are not rare and can include spinal fluid leaks, infection, and catheter/pump malfunction.
CASE PRESENTATION
This study presents information related to an adult male patient with traumatic SCI and a history of two prior ITB pump pocket infections that required removal due to pump infection. The patient then developed skin erosion over the third pump, and the fluid around the pump grew methicillin-sensitive Staphylococcus aureus, diphtheroids, and Candida parapsilosis. The patient was initially treated with antibiotics and anti-fungal medication without removal of the ITB pump. The ITB pump was eventually removed 27 months later, and the fourth pump was implanted 10 months later.
DISCUSSION
ITB pumps can be an effective treatment modality for spasticity in people with SCI; however, complications, including infection, can occur and require pump removal. This case illustrates a case of possible Candida colonization of the ITB pump, which was eventually removed.
Topics: Adult; Humans; Male; Baclofen; Muscle Relaxants, Central; Candida parapsilosis; Cervical Cord; Infusion Pumps, Implantable; Spinal Cord Injuries; Muscle Spasticity
PubMed: 38036498
DOI: 10.1038/s41394-023-00610-5 -
BMC Cardiovascular Disorders Jan 2024Cardiac resynchronization therapy (CRT) has been a well-established treatment modality for moderate to severe left ventricular systolic dysfunction with left ventricular... (Observational Study)
Observational Study
Clinical characteristics and outcome of cardiac resynchronization therapy for heart failure in National Hospital of Sri Lanka from year 2005 to 2020 - a retrospective observational study.
BACKGROUND
Cardiac resynchronization therapy (CRT) has been a well-established treatment modality for moderate to severe left ventricular systolic dysfunction with left ventricular desynchrony. This is the pioneering study that analyses the cohort who underwent CRT implantation at the National Hospital of Sri Lanka (NHSL) in Colombo from 2005 to 2020.
OBJECTIVES
This study was carried out to describe socio-demographic factors, improvements in clinical outcome (symptoms, electrocardiographic, and echocardiographic features), and post-CRT complications in the study population, as well as to determine the efficacy of CRT in heart failure.
METHOD
A retrospective observational study was conducted on all the living patients who had undergone CRT implantation from 2005 to 2020. The data was gathered from all the consented patients who visited the device programming clinic using a physician-administered questionnaire and clinical records. Data was analyzed using SPSS 25, and significant statistics were assessed with the McNemer test, the Student T test, and the Chi-Squared test.
RESULTS
The study included 50 patients with a mean age of 52.82+/- 11.66 years and female predominance (56%, n = 28). Idiopathic dilated cardiomyopathy (50%, n = 25) was the leading etiological factor, followed by ischemic cardiomyopathy (28%, n = 14). Clinical symptoms have improved significantly with CRT implantation (p < 0.001). A significant improvement was found in NYHA functional class (p < 0.001, 95% CI = 0.072 to 0.284), QRS width (p < 0.001, 95% CI = 0.229 to 0.534), ejection fraction (p < 0.001, 95% CI = - 16.437 to - 8.504), and LV EDD (p < 0.001, 95% CI = 2.89 to 9.24). Post-CRT complications included lead malfunction (6%, n = 3) and chronic (14%, n = 7), bleeding or hematoma (2%, n = 1), pocket erosion or infection (6%, n = 3), and infective endocarditis (2%, n = 1).
CONCLUSION
According to the study, CRT significantly improves both clinical and functional outcomes in patients with moderate to severe heart failure.
Topics: Humans; Female; Adult; Middle Aged; Male; Cardiac Resynchronization Therapy; Sri Lanka; Heart Failure; Ambulatory Care Facilities; Hospitals
PubMed: 38262994
DOI: 10.1186/s12872-024-03719-z -
Indian Heart Journal 2024Single chamber atrial pacemaker should be sufficient for patients with sinus node dysfunction (SND) with normal atrioventricular (AV) conduction. However, most patients...
BACKGROUND
Single chamber atrial pacemaker should be sufficient for patients with sinus node dysfunction (SND) with normal atrioventricular (AV) conduction. However, most patients undergo dual chamber pacemaker implantation because of concern of new onset AV block. The annual incidence of new AV block has been reported from 0.6 to 4.4 % in various studies.
OBJECTIVES
Our aim is to assess mode survival in sinus node dysfunction with normal AV conduction patients implanted with AAIR.
METHODS
Patients who underwent single chamber atrial pacemaker implantation for SND with normal AV conduction between January 2014 and December 2021 were followed up for pacemaker device change, new onset AV block, bundle branch block, atrial fibrillation (AF), lead complications, reoperation and mortality rate.
RESULTS
A total of 113 patients underwent single chamber atrial pacemaker implantation for SND during the study period. Mean age was 55.6 ± 12.7 years. During a mean follow up of 48.7 ± 24.9 months, none of the patients required pacemaker device change to VVIR/DDDR. Nine patients underwent reoperation, 5 for lead dislodgment, 1 for high threshold, 1 for pocket site erosion and 3 for pulse generator change. None developed AV block or AF with slow ventricular rate. Only 4 patients developed AF (3 paroxysmal,1 permanent). There were 3 deaths during follow up and none were sudden deaths.
CONCLUSION
Single chamber atrial pacing is an acceptable mode of pacing in patients with SND in developing countries. Development of AV conduction abnormalities is rare in this relatively younger population.
Topics: Humans; Adult; Middle Aged; Aged; Sick Sinus Syndrome; Atrioventricular Block; Cardiac Pacing, Artificial; Pacemaker, Artificial; Heart Atria; Atrial Fibrillation
PubMed: 38070672
DOI: 10.1016/j.ihj.2023.12.004 -
Journal of Cardiovascular... Mar 2024Patients with congenital heart disease are at increased risk for requiring cardiac pacing during their lifetime.
Different leadless pacemakers working in harmony (Aveir in the atrium/Micra AV2 in the ventricle) in a patient with dextrocardia and double outlet right ventricle after high-risk infected device extraction.
INTRODUCTION
Patients with congenital heart disease are at increased risk for requiring cardiac pacing during their lifetime.
METHODS
We present the first described case of using two leadless pacing systems manufactured by separate companies implanted within the same patient to provide atrial and ventricular pacing due to complex congenital anatomy.
RESULTS
A 27-year-old male with dextrocardia with double outlet right ventricle, subaortic ventricular septal defect, and pulmonary stenosis status-post pulmonary valve replacement complicated by ventricular pacing dependence and subsequent atrial pacing dependence after atriotomy-based atypical flutter ablation developed recurrent mediastinitis and pocket infection with erosion despite prolonged antibiotic treatment. Due to atrial and ventricular pacing dependence, a comprehensive congenital care team concluded the need for lead extraction and replacement of pacemaker via leadless peacemaking device. Laser-lead extraction and temporary atrial pacemaker placement was performed. Afterward, a transesophageal echocardiogram guided implantation of both a Micra AV 2 (Medtronic) leadless pacemaker in the interventricular septum within the right ventricle and an Aveir (Abbott) leadless pacemaker in the superior base of the right atrial appendage was performed with successful pacing. Although there is no communication between these devices, atrial-mechanical ventricular pacing was reliable with good implant thresholds, impedances and sensing from both devices.
CONCLUSION
Our case demonstrates the feasibility of using dual leadless pacing modalities to simultaneously pace someone at complex, prohibitive risk for temporary permanent or permanent pacemaker devices.
Topics: Male; Humans; Adult; Cardiac Pacing, Artificial; Heart Ventricles; Double Outlet Right Ventricle; Treatment Outcome; Pacemaker, Artificial; Dextrocardia; Equipment Design
PubMed: 38213071
DOI: 10.1111/jce.16173