Mode of coronary revascularization and short term clinical outcomes in patients with chronic kidney disease

Abstract BACKGROUND AND OBJECTIVE: Percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery are two alternative methods for coronary revascularization, but it remains controversial as which one is associated with lower risks of worse clinical outcomes for chronic kidney disease (CKD) patients. We determined the mode of coronary revascularization (PCI vs. CABG) which is associated with lower risk of mortality and morbidity in CKD patients. METHODS: In this cross sectional study, 159 patients with CKD were enrolled from single center of coronary revascularization at Aga Khan University Hospital Karachi between January 2012 and August 2013. All patients with CKD underwent PCI or CABG. The primary outcome was in-hospital composite of death, myocardial infarction (MI), or stroke. We evaluated which mode of coronary revascularization was associated with reduced risks of clinical outcomes. RESULTS: Out of 159 patients with CKD, 85 (53.5%) received PCI and 74 (46.5%) received CABG. The primary finding of this study is that more patients with moderate to severe CKD underwent PCI and more patients with mild to moderate CKD underwent CABG. In both these categories, no difference was observed in clinical outcomes. There are few factors like age, ST- elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) and number of coronary artery disease predicted PCI as treatment strategy in patients with moderate to severe CKD. CONCLUSION: Patients with moderate to severe CKD have similar rates of short term clinical outcomes whether they underwent PCI or CABG. Therefore, PCI can be acceptable and less invasive treatment option alternative to CABG, particularly in patients with moderate to severe CKD

Exercise as a treatment modality for depression: A narrative review

Depression is a major health burden associated with poor quality of life and impaired functioning. Depression is a leading cause of disability worldwide and is associated with profound economic costs. Depression is usually treated with antidepressant medications and psychological therapy or combination of both. However, there are lot of limitations associated with these therapies and as a result, a number of alternative or adjunctive therapies have been sought for. Exercise is one such option with a lot of substantial supportive research. The objective of the article was to review the beneficial effects of exercise in depression. An electronic search of literature from inception till 06/2017 highlighting the effects of exercise on depression and the possible mechanistic pathways involved was conducted using PubMed/ Medline, Google scholar and Scopus and relevant articles were utilized for this review. The results of this review confirmed the beneficial role of exercise in depression as evidenced by the improvement in the outcomes and the various psychobiological parameters measured. Thus exercise can be considered as a treatment option for the management of depression.Keywords: Depression, Exercise, Physical activity, Mechanistic pathways, BDN

Structural and micro-anatomical changes in vertebrae associated with idiopathic-type spinal curvature in the curveback guppy model

Background: The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature thatdevelops during growth. Prior work has revealed several important developmental similarities to the human idiopathicscoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that areassociated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a femalebias for severe curve magnitudes in the population.Methods: Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males andfemales. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variancetested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature,sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize microarchitecturalchanges in affected vertebrae and the intervertebral region.Results: In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion,migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexualdimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than domales. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reducedwidth at the middle of their vertebrae, relative to males.Conclusions: Based on similarities to human spinal curvatures and to animals with induced curves, the concaveconvexbiases described in the guppy suggest that there is a mechanical component to curve pathogenesis incurveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similarto Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanicalcomparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature incurveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics.Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the femalebias for severe curves that is observed in the population

RACK1 Is a Ribosome Scaffold Protein for β-actin mRNA/ZBP1 Complex

In neurons, specific mRNAs are transported in a translationally repressed manner along dendrites or axons by transport ribonucleic-protein complexes called RNA granules. ZBP1 is one RNA binding protein present in transport RNPs, where it transports and represses the translation of cotransported mRNAs, including β-actin mRNA. The release of β-actin mRNA from ZBP1 and its subsequent translation depends on the phosphorylation of ZBP1 by Src kinase, but little is known about how this process is regulated. Here we demonstrate that the ribosomal-associated protein RACK1, another substrate of Src, binds the β-actin mRNA/ZBP1 complex on ribosomes and contributes to the release of β-actin mRNA from ZBP1 and to its translation. We identify the Src binding and phosphorylation site Y246 on RACK1 as the critical site for the binding to the β-actin mRNA/ZBP1 complex. Based on these results we propose RACK1 as a ribosomal scaffold protein for specific mRNA-RBP complexes to tightly regulate the translation of specific mRNAs

SOX2 Co-Occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State

SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors

Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF

Long-term follow-up and donor site changes evaluation in suction blister epidermal grafting done for stable vitiligo: A retrospective study

Background: Suction blister epidermal grafting (SBEG) is one of the most commonly performed types of vitiligo surgery for stable vitiligo. The advantages of SBEG include cost-effectiveness and a relatively easier learning curve for the surgeon. Aims: To evaluate the outcome in terms of both recipient and donor site changes, on long-term follow-up of the patients who underwent SBEG in our center. Methods: Thirty patients, 21 females and 9 males ages ranging from 9 to 55 years, all having either stable vitiligo not responding to medical line of treatment, were included in the study done which involved a variable follow-up period ranging from 2 to 62 months (mean 23.6, standard deviation 17.79). SBEG was done as day care procedure. The patients were reviewed after 1-week and thereafter followed-up in the subsequent months and years. The results of the procedures were graded as poor (0-24%), fair (24-64%), good (64-94) and excellent (95-100%) depending on the patient satisfaction. Donor site changes were also analyzed. Results: The face and lips showed an excellent result and color match and persistent pigment retention. The larger areas, especially the lesions on the limbs showed comparatively less response. Of the total, 6.7% showed poor, 13.3% fair, 30% good and 50% excellent response to treatment. Patient satisfaction wise, 53.3% of the patients were very happy, 26.7% were happy, 10% satisfied and 10% unhappy. Significant positive correlation between patient satisfaction and physician observation was seen (Spearman′s rho 0.866). Conclusions: In spite of recent advances in surgical modalities like cellular grafting, SBEG continues to be a good, cost-effective, surgical method of treating vitiligo especially on the face and lip. The donor site also tends to show good healing tendency with minimal scarring and postinflammatory pigmentation