Keeping it in the family: Use of the grandmother,mother, and child technique to navigate complex anatomy during Coronary sinus Reducer Implantation

The Coronary Sinus Reducer® (CSR) is an emerging therapy for refractory angina recommended once no further pharmacologic or coronary revascularization options are available. We present the case of a 72-year-old man who underwent CSR implantation. Complex coronary sinus anatomy necessitated an innovative “grandmother, mother, and child” catheter approach.     

Role of tumor necrosis factor-alpha in the differential diagnosis of parapneumonic effusion.

OBJECTIVE: This study was undertaken to investigate the role of tumor necrosis factor-a (TNF-a) in discriminating between uncomplicated parapneumonic effusion (UCPPE) and complicated parapneumonic effusion (CPPE). METHOD: Using a commercially available high sensitivity enzyme-linked immunosorbent assay (ELISA) kit, concentrations of TNF were measured in the serum (TNFs) and pleural fluid (TNFpf) of 21 patients with parapneumonic effusion (PPE), 13 patients with UCPPE, and 8 patients with nonempyemic CPPE. RESULTS: No significant difference in values of TNF concentration was found between the group with UCPPE and that with CPPE (P > 0.05). Concentration levels of TNFpf were significantly higher in the group with CPPE than in that with UCPPE (P = 0.0008). Levels of TNF in pleural fluid were significantly higher than in serum in both groups (P < 0.001). The ratio of TNF in pleural fluid to that in serum (TNFr) was significantly higher in the CPPE group than in the UCPPE group (P = 0.0002). At an optimal cutoff point of 10.7 pg/mL for TNFpf, the sensitivity was 87.5%, specificity was 92.3%, positive predictive value was 87.5%, negative predictive value was 93.3%, and total accuracy was 90.5% (P < 0.001). At an optimal cutoff point of 3.0 for TNFr, all values were 100% (P < 0.00001). CONCLUSIONS: The results of this study indicate that TNFpf, and particularly TNFr, may be helpful in discriminating between UCPPE and CPPE. However, further studies are needed in a larger population to confirm these findings.     

Pamidronate treatment in rheumatology practice: a comprehensive review

Pamidronate, along with other bisphosphonates, has been used for treatment of bone pain secondary to malignant involvement or metastatic disease for years. Some data, however, have also accumulated on the utility of pamidronate in a variety of benign conditions frequently handled by rheumatologists. This study aims to review the available published data regarding the potential use of pamidronate in rheumatology practice. Methods include the review of relevant articles retrieved by a PUBMED search utilizing the index term “pamidronate”. All available randomized control trials, open trials, and case series, as well as properly reported case studies evaluating usage of pamidronate in rheumatic disorders, have been included in the literature review. The efficacy of pamidronate in patients with spondyloarthropathies; synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome; hypertrophic osteoarthropathy; osteoporotic vertebral fractures; chronic back pain due to disk disease or spinal stenosis; Charcot arthropathy; transient osteoporosis; and complex regional pain syndrome-I, has been demonstrated in more than 40 reports, the majority of which, however, were not controlled studies. In some of reviewed conditions, aside from providing analgesic relief, pamidronate may also have disease-modifying properties. While used in different doses in a variety of rheumatic disorders, pamidronate was generally reported to be well tolerated with an overall good safety profile. Pamidronate may represent an effective and safe choice for a spectrum of rheumatic patients, suffering from intractable musculoskeletal pain, unresponsive to traditionally recommended therapies. Large randomized, controlled studies examining the efficacy of pamidronate in the rheumatic conditions are urgently needed.     

Rheumatoid arthritis patients with interstitial lung disease: Clinical,radiological and laboratory characteristics

BackgroundRheumatoid arthritis associated interstitial lung disease (RA-ILD) has a significant burden of morbidity and mortality.Aim of the workTo analyze clinical, radiological and laboratory characteristics of RA-ILD in an Egyptian cohort.Patients and methodsThe study included 160 RA patients. Detailed medical history, disease activity score (DAS28) and joint damage (Sharp score) were carefully recorded. Chest x-ray, high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) were done and patients were sub-grouped as RA-ILD (HRCT or PFTs abnormalities) and RA without ILD.ResultsPatients were 136 (85%) females and 24 (15%) males with a mean age of 37.8 ± 11.3 years and disease duration of 4.98 ± 5.53 years. 50% of patients had chest manifestations suggestive of ILD. 60% demonstrated abnormalities in PFT and 63.75% in HRCT. The most common HRCT findings were reticulation (66.6%) and ground glass appearance (64.7%), followed by bronchiectasis (50.9%) and honey combing (46%). usual interstitial pneumonia (UIP) was the most common HRCT subtype (49%). RA-ILD patients were significantly older (p < 0.001), had longer disease duration (p < 0.001), more frequent arthritis (p = 0.002), higher DAS28 (p < 0.001) and Sharp score (p < 0.001), significantly positive rheumatoid factor (RF) (p = 0.007) and anti-citrullinated protein antibody (ACPA) (p < 0.001).ConclusionA high frequency of ILD among Egyptian patients is recorded due to careful evaluation of respiratory symptoms and valuable assessment by PFTs and HRCT chest. UIP is the most common radiologic pattern of RA-ILD. RA patients with ILD are significantly older with longer disease duration, delayed age at onset, high disease activity with arthritis and positive RF and ACPA.     

Depression in Behçet’s disease patients: Relationship with disease pattern,activity and quality of life

Aim of the workTo determine the frequency of depression in Behçet’s disease (BD) patients and to clarify its burden on patients’ clinical manifestations, disease activity status and quality of life (QoL).Patients and methods35 BD patients with 35 matched control were included in this study. Disease activity was assessed by Behçet Syndrome Activity Score (BSAS). All participants were requested to complete the Hamilton depression rating scale (HDRS), Multidimensional assessment of fatigue (MAF) questionnaire and the short form-36 (SF-36) QoL Scale.ResultsThe mean age of the patients was 40.3 ± 13.5 years (17–72 years) and they were 27 males and 8 females. The frequency of depression in BD patients was 74.3% with increased male frequency (p = 0.007) and major organ involvement (p = 0.04) among depressed patients. Significant differences (p < 0.001, p = 0.04, p = 0.001 respectively) between depressed and non depressed BD patients with respect to BSAS, MAF and SF-36. Highly significant positive correlations between HDRS and number of major organ, BSAS, MAF, (p < 0.001) and significant correlation with number of non major organs (r = 0.3, p = 0.04). Significant negative associations were observed between HDRS and SF-36 (r = ?0.6, p < 0.001). On regression number of major organ involvement (p < 0.001), BSAS (p = 0.01), MAF (p = 0.002), and SF-36 QoL (p < 0.001) significantly correlated with HDRS.ConclusionDepression is a significant comorbidity in patients with BD and is closely related to fatigue, number of major organ involvement and overall disease activity with a negative impact on QoL. Therefore, early interference and depression management in routine clinical practice is important to reduce patients’ symptoms, and improve QoL.     

Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease: Primary Results of the International Multicenter iFR GRADIENT Registry

Objectives

The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings.

Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC?+?CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p?<?0.0001, OR?=?4.9, 95% CI?=?2.7–8.8; p ? 0.0001, OR?=?3.6, 95% CI?=?2.2–5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC?+?CC) genotypes and C-allele compared with controls (p ? 0.0001, OR?=?5.1, 95% CI?=?2.7–9.7; p ? 0.0001, OR?=?3.5, 95% CI?=?2.1–6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p ? 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.     

Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

Lipid droplets (LDs) are intracellular organelles responsible for lipid storage, and they emerge from the endoplasmic reticulum (ER) upon the accumulation of neutral lipids, mostly triglycerides (TG), between the two leaflets of the ER membrane. LD biogenesis takes place at ER sites that are marked by the protein seipin, which subsequently recruits additional proteins to catalyze LD formation. Deletion of seipin, however, does not abolish LD biogenesis, and its precise role in controlling LD assembly remains unclear. Here, we use molecular dynamics simulations to investigate the molecular mechanism through which seipin promotes LD formation. We find that seipin clusters TG, as well as its precursor diacylglycerol, inside its unconventional ring-like oligomeric structure and that both its luminal and transmembrane regions contribute to this process. This mechanism is abolished upon mutations of polar residues involved in protein–TG interactions into hydrophobic residues. Our results suggest that seipin remodels the membrane of specific ER sites to prime them for LD biogenesis.

Lipid droplets (LDs) are the intracellular organelles responsible for fat accumulation (1). As such, they play a central role in lipid and cellular metabolism (1–4), and they are crucially involved in metabolic diseases such as lipodystrophy and obesity (5–7).Formation of LDs occurs in the endoplasmic reticulum (ER), where neutral lipids (NLs), namely triglycerides (TG) and cholesteryl esters, constituting the core of LDs are synthesized by acyltransferases that are essential for LD formation (8). The current model of LD formation posits that NLs are stored between the two leaflets of the ER bilayer, where they aggregate in nascent oblate lens-like structures with diameters of 40 to 60 nm (9) before complete maturation and budding toward the cytosol (10–13).Recent experiments suggest that LDs form at specific ER sites marked by the protein seipin (14) upon arrival of its interaction partner protein promethin/LDAF1 (lipid droplet organization [LDO] in yeast) (15–19). These recent observations confirm previous works showing that seipin, in addition to modulating LD budding and growth (14, 19–21) and LD–ER contacts (22, 23), is also a major player in the early stages of LD formation, as deletion of seipin leads to TG accumulation in the ER and a delay in the formation of, possibly aberrant, LDs (20, 24).The role of seipin in LD formation is potentially coupled to its function in regulating lipid metabolism (25, 26) and notably that of phosphatidic acid (PA) (27–31). Recently, seipin-positive ER loci have been shown to be part of a larger protein machinery that also includes membrane and lipid remodeling proteins of the TG synthesis pathway (32), most notably, Lipin (Pah1 in yeast) and FIT proteins (Yft2 and Scs3 in yeast), for which PA is either a known substrate (Lipin/Pah1) (33) or a likely one (FIT/Yft2/Scs3) (34).Despite this thorough characterization of the cellular role of seipin in LD formation, the molecular details of its mechanism remain mostly unclear. Recently, the structure of the luminal part of the seipin oligomer has been solved at 3.7 to 4.0 Å resolution using electron microscopy (27, 35), paving the way for the investigation of the relationship between its three-dimensional structure and its mode of action. These studies revealed that the luminal domain of seipin consists of an eight-stranded beta sandwich, together with a hydrophobic helix (HH), positioned toward the ER bilayer. Notably, the seipin oligomer assembles into a ring-like architecture, an unconventional assembly in lipid bilayers that rather resembles the shape of microbial pore-forming assemblies (36) or GroEL-GroES chaperones (37, 38).From a stochiometric point of view, both fluorescence and electron microscopy data are consistent with the presence of a single seipin oligomer per nascent LD (14, 15). Hence, the structure of the luminal part of seipin is consistent with two proposed modes of action: seipin could mark the sites of LD formation by controlling TG flow in and out of the nascent droplet (14), or, alternatively, seipin could help recognize and stabilize preexisting nascent droplets in the ER membrane (20, 21, 39). In both cases, however, the relationship between the role of seipin in LD formation and its ability to regulate lipid metabolism remains unclear.Here, we use coarse-grain (CG) molecular dynamics (MD) simulations to investigate the mechanism of seipin in molecular detail. We find that seipin is able to cluster TG molecules inside its ring-like structure and that both the transmembrane (TM) helices and the luminal domain contribute to this process. Diacylglycerol (DG), the lipid intermediate between TG and PA in the Kennedy pathway, also accumulates around seipin, further promoting the accumulation of TG at very low TG-to-phospholipids ratios. Our data suggest that by accumulating DG and TG molecules, seipin generates ER sites with a specific lipid composition that in turn could promote the sequential recruitment of additional TG- and DG-sensing proteins involved in LD formation, including promethin/LDOs, FIT/Yft2/Scs3, and perilipins.