Pancreatic ductal adenocarcinoma (PDAC) is the eighth largest cause of cancer-related mortality across the world, with a median 5-year survival rate of less than 3.5%. This is partly because the molecules and the molecular mechanisms that contribute to PDAC are not well understood. Our goal is to understand the role of p21-activated kinase 1 (Pak1) signaling axis in the progression of PDAC. Pak1, a serine/threonine kinase, is a well-known regulator of cytoskeletal remodeling, cell motility, cell proliferation and cell survival. Recent reports suggest that Pak1 by itself can have an oncogenic role in a wide variety of cancers. In this study, we analyzed the expression of Pak1 in human pancreatic cancer tissues and found that Pak1 levels are significantly upregulated in PDAC samples as compared with adjacent normals. Further, to study the functional role of Pak1 in pancreatic cancer model systems, we developed stable overexpression and lentiviral short hairpin RNA-mediated knockdown (KD) clones of Pak1 and studied the changes in transforming properties of the cells. We also observed that Pak1 KD clones failed to form tumors in nude mice. By adopting a quantitative PCR array-based approach, we identified fibronectin, a component of the extracellular matrix and a mesenchymal marker, as a transcriptional target of Pak1 signaling. The underlying molecular mechanism of Pak1-mediated transformation includes its nuclear import and recruitment to the fibronectin promoter via interaction with nuclear factor-κB (NF-κB)-p65 complex. To our knowledge, this is the first study illustrating Pak1-NF-κB-p65-mediated fibronectin regulation as a potent tumor-promoting mechanism in KRAS intact model.
Arteriovenous fistulas are an important means of vascular access for long-term haemodialysis in patients with end-stage renal disease (ESRD). We evaluated the outcome of radiocephalic arteriovenous fistulas (RCAVFs) in 55 patients operated upon in our hospital in southern India. We studied the outcome of RCAVF surgery with the demographic factors, duration of diabetes, the diameter of the radial artery and cephalic vein, and any signs of atherosclerosis in the radial artery. We found that a small cephalic vein size of ≤ 2 mm, a negative cephalic vein tap test, a thickened, non-compressible, calcified radial artery on palpation, and evidence of atherosclerosis on radiological investigations were associated with a significant chance of RCAVF failure. A clinico-radiological grading of atherosclerosis for peripheral arteries is also proposed. Any patient presenting to the microsurgeon with a small cephalic vein size, a negative cephalic vein tap test, a thickened, non-compressible, calcified vessel on palpation, and tram-track calcification or whole vessel calcification or severely atherosclerotic vessel on radiological evaluation must be approached with caution regarding RCAVF creation and must be prepared for an arteriovenous fistula (AVF) creation at a higher level.
Background: Fat grafting was developed in recent years with refinement mainly based on Coleman technique. The method consists of taking fat removed by liposuction under low pressure, fat processing and then placement of fat on the treated area.Methods: Patients who presented with depressed or retracted scars were considered. 12 patients were selected for the study as one year. Patients were given fat injection by Coleman’s technique and were evaluated at 1, 3 and 6 months. Patient and observer scar assessment score (POSAS) was used for evaluation.Results: The present study infers that there is a significant decrease in POSAS score on both the patient and observer side after fat injection for retracted scars. The overall patient score decreased from 5.75 (±0.866 SD) pre-operatively to 3.17 (±1.115 SD) post-operatively with a p value of less than 0.005. The difference between the scores is 2.58 which are comparable to other studies. The overall observer score decreased from 4.25 (±1.422 SD) pre-operatively to 2.58 (±0.996) post-operatively with a p value of less than 0.005. The difference between the scores is 1.67 which is comparable to other studies.Conclusions: Autologous fat grafting seems to be a promising and effective therapeutic approach for scars with different origins such as trauma, burns, post-surgery. In general, we can affirm that treated areas regain characteristics similar to normal skin, which are clinically perceptible, leading not only to aesthetic but also functional results.
A new classification for acquired split earlobes based on surgical implications is proposed here. Numerous techniques have been described and the choice of the surgery is a difficult one so a simplified approach to the choice of the repair method is provided. Any surgical repair, to stand the test of time must be simpler to perform and should serve the purpose of aesthetics as well as function. The composite method of earlobe repair described here incorporates an upper triangular flap preserving the perforation; the undermining of cleft margins to prevent suture line grooving, and a lower L-plasty to prevent inferior notching. This technique is easy to understand and perform, and avoids a second appointment and visit for ear piercing.
Background: Exact aetiology for keloid formation is yet unknown. The prime goal of the therapy is to decrease the process of scarring. Many modalities of treatment are available for keloids. With current treatment modalities, recurrence rates approaches 75%. This study was conducted to find out whether application of Epidermal growth factor will reduce recurrence rates of keloids, after surgical excision.Methods: An observational study was conducted by collecting details of 40 patients who underwent surgical excision of keloids followed by epidermal growth factor application over the wounds. The patients have been followed up to 6th months post excision and recurrence rates of keloids as well as overall scar quality were analysed.Results: Out of 45 patients included in the study, 16 (35.6 %) were males and rest females. The median age of the study population was 18.0 (with an IQR 16.0; 26.0). Out of 45 patients, 12 patients had family history of keloids (73%). Out of 45 patients, 8 had keloid tendency which amounts to 82%. Out of 45 patient who underwent treatment, 22 patient developed recurrence which is 48.9% Out of 45 patients included in the study, 16 (35.6 %) were males and rest females. The median age of the study population was 18.0 (with an IQR 16.0; 26.0). Out of 45 patients, 12 patients had family history of keloids (73%). Out of 45 patients, 8 had keloid tendency which amounts to 82%. Out of 45 patient who underwent treatment, 22 patient developed recurrence which is 48.9%.Conclusions: There is a dearth of randomized controlled trials supporting the efficacy of epidermal Growth factor in preventing keloid recurrence. The subjective improvements seen in some cases are encouraging. This study will be a foundation for future studies and will highlight the breadth of knowledge yet to be explored by this therapy.
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