Integrative miRNA-mRNA network analysis to identify crucial pathways of salinity adaptation in brain transcriptome of Labeo rohita.

Introduction: Brain being the master regulator of the physiology of animal, the current study focuses on the gene expression pattern of the brain tissue with special emphasis on regulation of growth, developmental process of an organism and cellular adaptation of Labeo rohita against unfavourable environmental conditions. Methods: RNA-seq study was performed on collected brain samples at 8ppt salt concentration and analyzed for differential gene expression, functional annotation and miRNA-mRNA regulatory network. Results: We found that 2450 genes were having significant differential up and down regulation. The study identified 20 hub genes based on maximal clique centrality algorithm. These hub genes were mainly involved in various signaling pathways, energy metabolism and ion transportation. Further, 326 up and 1214 down regulated genes were found to be targeted by 7 differentially expressed miRNAs i.e., oni-miR-10712, oni-miR-10736, ssa-miR-221-3p, ssa-miR-130d-1-5p, ssa-miR-144-5p and oni-miR-10628. Gene ontology analysis of these differentially expressed genes led to the finding that these genes were involved in signal transduction i.e., calcium, FOXO, PI3K-AKT, TGF-ß, Wnt and p53 signalling pathways. Differentially expressed genes were also involved in regulation of immune response, environmental adaptation i.e., neuroactive ligand-receptor interaction, ECM-receptor interaction, cell adhesion molecules and circadian entrainment, osmoregulation and energy metabolism, which are critical for salinity adaptation. Discussion: The findings of whole transcriptomic study on brain deciphered the miRNA-mRNA interaction patterns and pathways associated with salinity adaptation of L. rohita.

Prophylactic Uterine Artery Embolization in Placenta Accreta Spectrum-An Active Intervention to Reduce Morbidity and Promote Uterine Preservation.

PURPOSE: To evaluate the feasibility and safety of early and proactive involvement of interventional radiology (IR) in the management of placenta accreta spectrum (PAS) by performing the cesarean operation and prophylactic uterine artery embolization in the IR angiography suite as a combined procedure. MATERIALS AND METHODS: This study evaluated the effectiveness and safety of prophylactic uterine artery embolization prior to placental separation in cases of antenatally proven or suspected abnormal placentation. Over a 5-year period, 16 consecutive patients with PAS underwent combined IR and obstetric intervention. In all cases, cesarean delivery was performed in the IR angiography suite. Vascular access was obtained prior to surgery with balloon placement into both internal iliac arteries. These balloons were inflated after delivery, followed by uterine artery embolization (14 of 16) if there was evidence of active postpartum bleeding or inability to deliver the placenta. RESULTS: There was no fetal or maternal mortality and no significant IR or surgical adverse events. Mean blood loss was 1900 mL. Seven patients (44%) underwent hysterectomy. CONCLUSIONS: In patients with PAS, cesarean section in the angiography suite preceded by prophylactic balloon placement and followed by uterine artery embolization was feasible, safe, and effective in preventing massive blood loss, with a 56% uterine sparing rate.

Interplay of gene expression and regulators under salinity stress in gill of Labeo rohita.

BACKGROUND: Labeo rohita is the most preferred freshwater carp species in India. The concern of increasing salinity concentration in freshwater bodies due to climate change may greatly impact the aquatic environment. Gills are one of the important osmoregulatory organs and have direct contact with external environment. Hence, the current study is conducted to understand the gill transcriptomic response of L. rohita under hypersalinity environment. RESULTS: Comprehensive analysis of differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs was performed in gills of L. rohita treated with 2, 4, 6 and 8ppt salinity concentrations. Networks of lncRNA-miRNA-mRNA revealed involvement of 20, 33, 52 and 61 differentially expressed lncRNAs, 11, 13, 26 and 21 differentially expressed miRNAs in 2, 4, 6 and 8ppt groups between control and treatment respectively. These lncRNA-miRNA pairs were regulating 87, 214, 499 and 435 differentially expressed mRNAs (DE mRNAs) in 2, 4, 6 and 8ppt treatments respectively. Functional analysis of these genes showed enrichment in pathways related to ion transportation and osmolyte production to cope with induced osmotic pressure due to high salt concentration. Pathways related to signal transduction (MAPK, FOXO and phosphatidylinositol signaling), and environmental information processing were also upregulated under hypersalinity. Energy metabolism and innate immune response pathways also appear to be regulated. Protein turnover was high at 8ppt as evidenced by enrichment of the proteasome and aminoacyl tRNA synthesis pathways, along with other enriched KEGG terms such as apoptosis, cellular senescence and cell cycle. CONCLUSION: Altogether, the RNA-seq analysis provided valuable insights into competitive endogenous (lncRNA-miRNA-mRNA) regulatory network of L. rohita under salinity stress. L. rohita is adapting to the salinity stress by means of upregulating protein turnover, osmolyte production and removing the damaged cells using apoptotic pathway and regulating the cell growth and hence diverting the essential energy for coping with salinity stress.

Kidney transcriptome response to salinity adaptation in Labeo rohita.

The increasing salinization of freshwater resources, owing to global warming, has caused concern to freshwater aquaculturists. In this regard, the present study is aimed at economically important freshwater fish, L. rohita (rohu) adapting to varying degrees of salinity concentrations. The RNA-seq analysis of kidney tissue samples of L. rohita maintained at 2, 4, 6, and 8 ppt salinity was performed, and differentially expressed genes involved in various pathways were studied. A total of 755, 834, 738, and 716 transcripts were downregulated and 660, 926, 576, and 908 transcripts were up-regulated in 2, 4, 6, and 8 ppt salinity treatment groups, respectively, with reference to the control. Gene ontology enrichment analysis categorized the differentially expressed genes into 69, 154, 92, and 157 numbers of biological processes with the p value < 0.05 for 2, 4, 6, and 8 ppt salinity groups, respectively, based on gene functions. The present study found 26 differentially expressed solute carrier family genes involved in ion transportation and glucose transportation which play a significant role in osmoregulation. In addition, the upregulation of inositol-3-phosphate synthase 1A (INO1) enzyme indicated the role of osmolytes in salinity acclimatization of L. rohita. Apart from this, the study has also found a significant number of genes involved in the pathways related to salinity adaptation including energy metabolism, calcium ion regulation, immune response, structural reorganization, and apoptosis. The kidney transcriptome analysis elucidates a step forward in understanding the osmoregulatory process in L. rohita and their adaptation to salinity changes.

A novel approach to treating a post-sternotomy internal mammary artery pseudoaneurysm.

Pseudoaneurysms of the internal mammary artery are a rare complication of median sternotomy. They may clinically present as a pulsatile mass or with signs of rupture and haemodynamic instability. In stable patients, percutaneous thrombin injection of the pseudoaneurysm is a safe and minimally invasive procedure to treat the pseudoaneurysm and avoid further surgery. We present a case of a pseudoaneurysm of a branch of the right internal mammary artery post-median sternotomy with no signs or symptoms of haemodynamic instability. The pseudoaneurysm was successfully treated with ultrasound-guided percutaneous thrombin injection.

Endovascular versus Open Repair of Asymptomatic Popliteal Artery Aneurysms: A Systematic Review and Meta-Analysis.

This systematic review compared outcomes between endovascular and open repair of asymptomatic popliteal artery aneurysms (PAAs). Endovascular repair was associated with increased 30-day graft occlusion (odds ratio [OR] = 3.14; 95% confidence interval [CI], 1.43-6.92) and increased 30-day reintervention (OR = 4.09; 95% CI, 2.79-6.00). The 12-month primary patency rate was significantly higher in the open repair group (hazard ratio = 1.95; 95% CI, 1.14-3.33). Endovascular repair was associated with shorter length of hospital stay (mean difference = -3 d; 95% CI, -4.09 to -1.91; P < .001). Endovascular repair is associated with inferior perioperative and postoperative outcomes compared with open repair.

Outcome following a negative CT Angiogram for gastrointestinal hemorrhage.

OBJECTIVE: This study was designed to evaluate the role of a negative computed tomography angiogram (CTA) in patients who present with gastrointestinal (GI) hemorrhage. METHODS: A review of all patients who had CTAs for GI hemorrhage over an 8-year period from January 2005 to December 2012 was performed. Data for patient demographics, location of hemorrhage, hemodynamic stability, and details of angiograms and/or the embolization procedure were obtained from the CRIS/PACS database, interventional radiology database, secure electronic medical records, and patient's clinical notes. RESULTS: A total of 180 patients had 202 CTAs during the 8-year period: 87 CTAs were performed for upper GI hemorrhage (18 positive for active bleeding, 69 negative) and 115 for lower GI hemorrhage (37 positive for active bleeding, 78 negative); 58.7 % (37/63) of patients with upper GI bleed and 77.4 % (48/62) of patients with lower GI bleed who had an initial negative CTA did not rebleed without the need for radiological or surgical intervention. This difference was statistically significant (p = 0.04). The relative risk of rebleeding, following a negative CTA, in lower GI bleeding versus upper GI bleeding patients is 0.55 (95 % confidence interval 0.32-0.95). CONCLUSIONS: Patients with upper GI bleed who had negative CTAs usually require further intervention to stop the bleeding. In contrast, most patients presenting with lower GI hemorrhage who had a negative first CTA were less likely to rebleed.

Is there a role for empiric gastroduodenal artery embolization in the management of patients with active upper GI hemorrhage?

PURPOSE: To assess the relative efficacy of empiric gastroduodenal artery (GDA) embolization in reducing recurrent hemorrhage compared to image-guided targeted embolization. METHODS: Data were retrospectively collected for consecutive patients who had catheter angiography for major upper gastrointestinal hemorrhage from May 2008 to November 2010 (n = 40). The total number of cases were divided into two main groups according to angiographic findings: those that demonstrated a site of hemorrhage on catheter angiography (group 1, n = 13), and those where the site of hemorrhage was not identified on catheter angiography (group 2, n = 27). Group 2 was then further divided into patients who received empiric embolization (group 2a, n = 20) and those who had no embolization performed after angiography (group 2b, n = 7). RESULTS: The technical and clinical success rates for embolization in groups 1 and 2a were, respectively, 100 vs. 95%, and 85 vs. 80%. There was no statistical significance in the recurrent hemorrhage rate, reintervention rate, or 30 day mortality between targeted and empiric embolization groups. There were no complications attributed to embolization within this study cohort. CONCLUSION: Cases of duodenal-related major upper gastrointestinal hemorrhage where no embolization is performed have poor outcome. Empiric embolization of the GDA in patients with major upper gastrointestinal hemorrhage refractory to endoscopic treatment appears to be a safe and effective treatment, with low reintervention rates and good clinical outcome comparable to patients where the site of hemorrhage is localized and embolized with computed tomographic angiography or catheter angiography and embolized.

A novel endovascular technique in the management of a large internal iliac artery aneurysm associated with an arteriovenous fistula.

PURPOSE: To describe a novel endovascular technique in the management of a complex arteriovenous fistula between a large internal iliac artery aneurysm and the adjacent iliac vein in a 76-year old patient with previous aortobifemoral bypass graft with an occluded proximal common iliac artery. CASE REPORT: Due to the high risk of open surgery in this case, endovascular treatment with simultaneous venous and arterial access was performed, with implantation of 2 stent grafts in the iliac vein to cover the fistulous communication and embolisation of the native external iliac artery (inflow). CONCLUSION: The endovascular technique described enables thrombosis of the large internal iliac aneurysm and treatment of the arteriovenous fistula without exposing the patient to the high morbidity and mortality associated with open surgery.

Static sac size with a type II endoleak post-endovascular abdominal aortic aneurysm repair: surveillance or embolization?

A best evidence topic was written according to a structured protocol. The question addressed was whether embolization is superior to surveillance for a type II endoleak associated with a static sac size post-endovascular abdominal aortic aneurysm repair (EVAR). Four hundred and sixty-one papers were identified, of which 10 papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, and relevant outcomes and results are tabulated. A review of the available literature suggests that most type II endoleaks are innocuous and will seal spontaneously during the long-term follow-up, even when they persist for more than 6 months. An analysis of the large European Collaborators on Stent-Graft Techniques for Aortic Aneurysm Repair (EUROSTAR) registry that includes prospective data on 2463 patients from 87 European hospitals showed that type II endoleaks were not associated with an increased risk of rupture; this correlates well with the large single-centre studies included in this review. Based on the available evidence, we conclude that the management of most isolated type II endoleaks should be conservative-with close radiological follow-up--even when persistent, with intervention restricted to theoese associated with sac enlargement >5 mm over a 6-month period or >10 mm when compared with pre-EVAR diameter.

Results of a seven-year, single-centre experience of the long-term outcomes of bovine ureter grafts used as novel conduits for haemodialysis fistulas.

PURPOSE: To report the long-term outcomes of bovine ureter grafts as novel conduits for haemodialysis fistulas. MATERIALS AND METHODS: Thirty-five patients underwent placement of a total of 40 SynerGraft 100 (SG100; CryoLife Europa(®), Guildford, UK) bovine ureter grafts between April 2002 and February 2009. Prospective data were collected on all patients, including active surveillance with blood flow studies and 6-monthly duplex ultrasound studies. Main outcome measures were primary and secondary patency rates. RESULTS: Mean follow-up time was 97 weeks (range 4-270). Thirteen patients died from unrelated causes during the study period; 12 of these patients had a functioning graft at the time of death. Five patients underwent transplantation, and all had a functioning graft at transplantation. Twelve patients had a functioning graft at the end of the study period. One hundred and ten stenoses were detected, and 97 venoplasty procedures were performed. Of the stenoses, 41.8% were located at the venous anastomosis, 12.7% within the graft, 17.3% in the outflow veins, and 28.1% in central veins. No arterial stenoses were detected. Primary patency rates were 53% at 6 months and 14% at 1 year. Secondary patency rates were 81% at 6 months, 75% at 1 year, and 56% at 2 years. CONCLUSIONS: Active surveillance and intervention was able to achieve satisfactory long-term secondary patency for these novel conduits compared with those made of PTFE seen in other studies [1].

Standard of practice for the interventional management of isolated iliac artery aneurysms.

Isolated iliac artery aneurysms are uncommon, comprising less than 2% of all abdominal aneurysmal disease. Although they have a fairly innocuous natural history, when they have attained a large size they carry a significant risk of rupture. Rupture is associated with significant morbidity and mortality. Therefore, an early diagnosis and treatment are crucial. Over the last decade, interventional treatment options have become established alternatives to open surgical repair. These guidelines aim to review the pathogenesis, natural history, and presentation of isolated iliac artery aneurysms including a description of imaging and interventional treatment strategies.

Development and in vitro evaluation of ibuprofen mouth dissolving tablets using solid dispersion technique.

The aim of present study was to prepare and evaluate mouth dissolving tablets of ibuprofen (IBU). Ternary solid dispersion (SD) of IBU was prepared using PEG 4000 as carrier and Tween 80 as surfactant. The SD formulations were prepared by solvent evaporation and melt solvent method by varying ratio of PEG 4000. Different weight ratio of carrier, drug and surfactant 5 : 5 : 1, 10 : 5 : 1, 25 : 5 : 1, 35 : 5 : 1 and 45 : 5 : 1 was taken. The prepared SD formulations were characterized by Fourier Transform Infra-Red (FT-IR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and in vitro drug release. Mouth dissolving tablets of IBU were formulated using optimized SD formulation of carrier : drug : surfactant ratio, 10 : 5 : 1 along with super-disintegrants. The best developed formulation was compared with marketed tablet product of IBU. From IR and XRD studies, it may be concluded that there is change in crystalline form of drug into amorphous during formation of SD. From DSC studies, it was predicted that drug was completely dissolved in the carrier. Mouth dissolving tablets containing Ac-Di-Sol (12%) as super-disintegrant showed the fastest disintegration (202s) and in vitro drug release (84.57%). The release pattern of all developed formulations followed Peppas-Korsmeyer model as the plot between log cumulative % drug released versus log time showed good linearity (r>0.99) with a comparatively high slope (n) value within the range of 0.44-0.67. The tablets containing SD exhibited better dissolution profile than commercial tablets.

Palliation of obstructing malignant colonic lesions using self-expanding metal stents: a single-center experience.

To evaluate the efficacy, risks, and survival after palliative colorectal stenting at a single center, we conducted a retrospective review of consecutive patients who had colorectal self-expanding metal stents (SEMSs) inserted over an 8-year period (September 1998 to September 2006) to relieve an obstructing colorectal tumor. All patients either had proven distant metastases or were unfit for surgical decompression. A single interventional radiologist (R.M.) inserted the stents, which were either Memotherm or WallFlex. Ninety-one patients with a median age of 73 years had a colorectal stent inserted for palliation of an obstructing colorectal malignancy. Technical success was achieved in 81 of 91 (89%) patients, and clinical success in 80 of 81 (99%). At the time of analysis (December 2006), 13 of 91 (14.2%) patients were alive. The patients who died had a median survival of 59 days, IQR 17-181 days. Seven (7/81) patients suffered stent migration, which occurred 10.3 days (IQR, 5-14 days) after the procedure. Three patients (3/81) re-presented with intestinal obstruction secondary to tumor ingrowth and 10 (10.9%) patients suffered bowel perforation. Ten patients (10.9%) had two stents inserted coaxially and overlapping in one procedure. This was performed in cases where the stricture was too long to be easily crossed by a single stent. We conclude that colorectal SEMS is a safe and effective mode of treatment for the palliation of obstructing colorectal cancers, which avoids high-risk surgery.

Is cardiac computed tomography a reliable alternative to percutaneous coronary angiography for patients awaiting valve surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether a CT angiogram could replace routine percutaneous coronary angiography for excluding coronary arterial disease for patients undergoing a non coronary cardiac procedure. Using the reported search 595 papers were identified. Eleven papers represented the best evidence on the subject and the author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated. We conclude that angiography with 64-slice multi-detector CT scanner provides reliable non-invasive imaging to exclude significant coronary artery stenoses prior to valve surgery. The negative predictive value of a normal CT scan is around 97%, thus providing a good alternative to conventional angiography in lower atherosclerotic risk patients. The ability of CT angiography to assess the reduction in luminal diameter is reduced in the presence of calcium deposits, and is also reduced in vessels under 1.5 mm. Further disadvantages include an inability to perform scans in patients with arrhythmias or atrial fibrillation, and a five times increased radiation dose compared to conventional angiography.

Anti-KC autoantibody:KC complexes cause severe lung inflammation in mice via IgG receptors.

We have shown previously that high concentrations of IL-8 associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes) are present in lung fluids from patients with the acute respiratory distress syndrome (ARDS), and correlate both with the development and outcome of ARDS. We also detected deposition of these complexes in lung tissues from patients with ARDS but not in control tissues. Moreover, we determined that IgG receptors (FcgammaRs) mediate activity of anti-IL-8:IL-8 complexes. In the current study, we generated anti-KC (KC = chemokine (CXC motif) ligand 1 (CXCL1)) autoantibody:KC immune complexes (KC-functional IL-8) in lungs of mice to develop a mouse model of autoimmune complex-induced lung inflammation. Both wild-type (WT) and gamma-chain-deficient mice that lack receptors for immune complexes (FcgammaRs) were studied. First, the mice were immunized with KC to induce anti-KC autoantibodies. Then, KC was administered intratracheally to generate anti-KC:KC complexes in the lung. Presence of anti-KC:KC complexes was associated with development of severe pulmonary inflammation that was, however, dramatically suppressed in gamma-chain-deficient mice. Second, because sepsis is considered the major risk factor for development of ARDS, we evaluated LPS-treated WT as well as gamma-chain-deficient mice for the presence of anti-KC:KC complexes and pulmonary inflammatory responses. We detected complexes between anti-KC autoantibodies and KC in lung lavages and tissues of mice treated with LPS. Moreover, gamma-chain-deficient mice that lack receptors for immune complexes were protected from LPS-induced pulmonary inflammation. Our results suggest that immune complexes containing autoantibodies contribute to development of lung inflammation in LPS-treated mice.

Above-knee vein harvest for coronary revascularization increases ASEPSIS score.

The long saphenous vein may be harvested from the thigh or the lower leg, depending on the operating surgeon's preference. This prospective study compared the incidence of altered wound healing between these two sites in 175 patients undergoing routine coronary artery bypass grafting over a 3-month period. The patients were divided into 3 groups. In group A, the vein harvest site was restricted to above the upper border of the patella. Group B included harvest sites that started at the ankle but extended above the level of the upper border of the patella. In group C, the vein harvest site was restricted to below the upper border of the patella. The wounds were assessed daily using the ASEPSIS scoring system. In group A, significantly more patients (24%) had an ASEPSIS score > 10, compared to group B (3%) and group C (2%). The mean ASEPSIS score was significantly lower in group C than groups A or B, 1.5 +/- 2.4 vs. 6.5 +/- 3.2 or 3.7 +/- 1.7, respectively. The ASEPSIS score is reduced when vein harvest is restricted to below the level of the knee.