SONG: A Multi-Objective Evolutionary Algorithm for Delay and Energy Aware Facility Location in Vehicular Fog Networks.

With the emergence of delay- and energy-critical vehicular applications, forwarding sense-actuate data from vehicles to the cloud became practically infeasible. Therefore, a new computational model called Vehicular Fog Computing (VFC) was proposed. It offloads the computation workload from passenger devices (PDs) to transportation infrastructures such as roadside units (RSUs) and base stations (BSs), called static fog nodes. It can also exploit the underutilized computation resources of nearby vehicles that can act as vehicular fog nodes (VFNs) and provide delay- and energy-aware computing services. However, the capacity planning and dimensioning of VFC, which come under a class of facility location problems (FLPs), is a challenging issue. The complexity arises from the spatio-temporal dynamics of vehicular traffic, varying resource demand from PD applications, and the mobility of VFNs. This paper proposes a multi-objective optimization model to investigate the facility location in VFC networks. The solutions to this model generate optimal VFC topologies pertaining to an optimized trade-off (Pareto front) between the service delay and energy consumption. Thus, to solve this model, we propose a hybrid Evolutionary Multi-Objective (EMO) algorithm called Swarm Optimized Non-dominated sorting Genetic algorithm (SONG). It combines the convergence and search efficiency of two popular EMO algorithms: the Non-dominated Sorting Genetic Algorithm (NSGA-II) and Speed-constrained Particle Swarm Optimization (SMPSO). First, we solve an example problem using the SONG algorithm to illustrate the delay-energy solution frontiers and plotted the corresponding layout topology. Subsequently, we evaluate the evolutionary performance of the SONG algorithm on real-world vehicular traces against three quality indicators: Hyper-Volume (HV), Inverted Generational Distance (IGD) and CPU delay gap. The empirical results show that SONG exhibits improved solution quality over the NSGA-II and SMPSO algorithms and hence can be utilized as a potential tool by the service providers for the planning and design of VFC networks.

Upregulated Angiogenesis Is Incompetent to Rescue Dilated Cardiomyopathy Phenotype in Mice.

Dilated cardiomyopathy (DCM) is characterized by pathologic cardiac remodeling resulting in chambers enlargement and impaired heart contractility. Previous reports and our in-silico analysis support the association of DCM phenotype and impaired tissue angiogenesis. Here, we explored whether the modulation in cardiac angiogenesis partly intervenes or rescues the DCM phenotype in mice. Here, a DCM mouse model [α-tropomyosin 54 (α-TM54) mutant] was crossbred with microRNA-210 transgenic mice (210-TG) to develop microRNA-210 (miR-210) overexpressing α-TM54 mutant mice (TMx210). Contrary to wild-type (WT) and 210-TG mice, a significant increase in heart weight to body weight ratio in aged mixed-gender TMx210 and DCM mice was recorded. Histopathological analysis revealed signs of pathological cardiac remodeling such as myocardial disarray, myofibrillar loss, and interstitial fibrosis in DCM and TMx210 mice. Contrary to WT and DCM, a significant increase in angiogenic potential was observed in TMx210 and 210-TG mice hearts which is reflected by higher blood vessel density and upregulated proangiogenic vascular endothelial growth factor-A. The echocardiographic assessment showed comparable cardiac dysfunction in DCM and TMx210 mice as compared to WT and 210-TG. Overall, the present study concludes that miR-210 mediated upregulated angiogenesis is not sufficient to rescue the DCM phenotype in mice.

A Case of Isolated Left Ventricular Non-Compaction Cardiomyopathy in a HIV Patient Presenting With Acute Heart Failure.

The etiology of cardiomyopathy in a HIV patient is multifactorial. Identifying the etiology of cardiomyopathy in a HIV patient needs extensive evaluation. Common causes include ischemic cardiomyopathy, myocarditis due to viral infections and opportunistic infections, cocaine abuse, alcoholic heart disease, drug toxicity or due to nutritional deficiencies. However, in a number of cases the etiology is unknown. We report a case of 36-year-old African American man with history of HIV who presented with acute heart failure due to left ventricular non-compaction (LVNC). Transthoracic and transesophageal echocardiogram showed significant left ventricular trabeculations and blood flow in deep recesses. Endomyocardial biopsy was suggestive of LVNC. He underwent left ventricular assist device implantation for destination therapy and subsequently cardiac transplantation. The diagnosis of LVNC is often made by echocardiogram. As LVNC could be a normal variant, a comprehensive diagnostic assessment including multimodality imaging, a systematic screening of first degree relatives, and a comprehensive clinical and genetic assessment by a multidisciplinary team may be needed to arrive at the diagnosis. Early diagnosis and timely intervention may reduce the risk of premature death in these young patients.

Frequent Sips of the Water for the Management of Gastroesophageal Reflux Induced Refractory Cough: A Case Report and Review of the Literature.

BACKGROUND: Chronic cough is often associated with gastroesophageal reflux disease (GERD). The role of gastroenterologist in the management of the chronic cough is to identify and manage GERD. Ineffective esophageal motility is often associated with GERD induced cough. Chronic cough is often refractory to medical and surgical management despite adequate acid control. Unresponsiveness warrants a thorough pulmonary evaluation. The pathophysiology of refractory cough in these patients is poorly understood, and hence management is often challenging. CASE PRESENTATION: A 75-year-old woman from Ghana was evaluated for GERD associated chronic cough. A 48-hour ambulatory pH study revealed acid exposure of 4.9% and high-resolution manometry showed decreased lower esophageal sphincter pressure, an inadequate response to medical and surgical management of GERD. Postfundoplication ambulatory pH testing demonstrated well-controlled acid reflux but her cough still persisted. Repeat manometry showed an ineffective motility disorder (IEM). Taking frequent sips of water eventually resolved her chronic cough. CONCLUSION: Frequent sips of water can be used in the management of the gastroesophageal reflux and ineffective motility induced cough. It results in increased esophageal clearance of acid, nonacid reflux, and ingested pharyngeal secretions, thus breaking the cycle of cough generated increased intra-abdominal pressure with reflux and more cough.

Inhibition of Senescence-Associated Genes Rb1 and Meis2 in Adult Cardiomyocytes Results in Cell Cycle Reentry and Cardiac Repair Post-Myocardial Infarction.

Background Myocardial infarction results in a large-scale cardiomyocyte loss and heart failure due to subsequent pathological remodeling. Whereas zebrafish and neonatal mice have evident cardiomyocyte expansion following injury, adult mammalian cardiomyocytes are principally nonproliferative. Despite historical presumptions of stem cell-mediated cardiac regeneration, numerous recent studies using advanced lineage-tracing methods demonstrated that the only source of cardiomyocyte renewal originates from the extant myocardium; thus, the augmented proliferation of preexisting adult cardiomyocytes remains a leading therapeutic approach toward cardiac regeneration. In the present study we investigate the significance of suppressing cell cycle inhibitors Rb1 and Meis2 to promote adult cardiomyocyte reentry to the cell cycle. Methods and Results In vitro experiments with small interfering RNA-mediated simultaneous knockdown of Rb1 and Meis2 in both adult rat cardiomyocytes, isolated from 12-week-old Fischer rats, and human induced pluripotent stem cell-derived cardiomyocytes showed a significant increase in cell number, a decrease in cell size, and an increase in mononucleated cardiomyocytes. In vivo, a hydrogel-based delivery method for small interfering RNA-mediated silencing of Rb1 and Meis2 is utilized following myocardial infarction. Immunofluorescent imaging analysis revealed a significant increase in proliferation markers 5-ethynyl-2'-deoxyuridine, PH3, KI67, and Aurora B in adult cardiomyocytes as well as improved cell survivability with the additional benefit of enhanced peri-infarct angiogenesis. Together, this intervention resulted in a reduced infarct size and improved cardiac function post-myocardial infarction. Conclusions Silencing of senescence-inducing pathways in adult cardiomyocytes via inhibition of Rb1 and Meis2 results in marked cardiomyocyte proliferation and increased protection of cardiac function in the setting of ischemic injury.

Small-Cell Type, Poorly Differentiated Neuroendocrine Carcinoma of the Gallbladder: A Case Report and Review of the Literature.

The poorly differentiated small-cell type, neuroendocrine carcinoma (NEC) of the gallbladder is a very uncommon subtype of a neuroendocrine tumor of the gastrointestinal tract. Nonsecretory NEC by virtue of its nonspecific and subtle clinical presentation of the tumor is usually diagnosed at an advance stage with presenting symptoms related to either locally advance disease or from metastatic disease. Though the radiologic imaging does identify the gall bladder cancer, the tumor lacks a specific diagnostic test; therefore, the diagnosis is almost always confirmed on histopathologic and immunohistochemical staining. We present a case of a poorly differentiated, small-cell neuroendocrine tumor of the gallbladder. The patient died within 3 months after the definitive diagnosis was made. Survival from this deadly malignancy can be improved with aggressive surgical treatment followed by chemotherapy and radiotherapy on a case-by-case scenario. The systemic chemotherapy remained the treatment of choice for an unresectable tumor (Chen et al., 2014).

Adenine acts in the kidney as a signaling factor and causes salt- and water-losing nephropathy: early mechanism of adenine-induced renal injury.

Chronic adenine feeding is extensively used to develop animal models of chronic renal failure with metabolic features resembling those observed in humans. However, the mechanism by which adenine induces renal failure is poorly understood. In this study, we examined the early effects of adenine on water metabolism and salt balance in rats placed in metabolic cages and fed control or adenine-containing diets for 7 days. Molecular and functional studies demonstrated that adenine-fed rats exhibited a significant reduction in food intake, polyuria, polydipsia, decreased urine osmolality, and increased salt wasting. These effects are independent of changes in food intake and result from a coordinated downregulation of water channel aquaporin-2 (AQP2) and salt transporter (Na+-K+-Cl- cotransporter 2; NKCC2) in the collecting duct and medullary thick ascending limb, respectively. As a result, adenine-fed rats exhibited massive volume depletion, as indicated by a significant body weight loss, increased blood urea nitrogen, and increased hematocrit and hemoglobin levels, all of which were significantly corrected with NaCl replacement. Adenine-induced urinary concentrating defect was not corrected by exogenous arginine vasopressin (AVP), and it correlated with reduced cAMP production in vivo and in vitro. In conclusion, adenine acts on renal tubules as a signaling molecule and causes nephrogenic diabetes insipidus with salt wasting, at least, by directly interfering with AVP V2 receptor signaling with subsequent downregulation of NKCC2 and AQP2 in the kidney. The combination of renal fluid loss and decreased food intake with subsequent massive volume depletion likely plays an important role in the development of early prerenal failure that progresses to chronic kidney disease in long-term adenine feeding.

Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review.

Neuroendocrine cells are widespread throughout the body and can give rise of neuroendocrine tumors due to abnormal growth of the chromaffin cells. Neuroendocrine tumors divide into many subtypes based on tumor grade (Ki-67 index and mitotic count) and differentiation. These tumors can be further divided into secretory and nonsecretory types based on the production of peptide hormone by tumor cells. Poorly differentiated small-cell-type neuroendocrine tumors are one of the subtypes of neuroendocrine tumors. These tumors are less common; however, they tend to be locally invasive and aggressive in behavior with poor overall median survival. Treatment of the nonsecretory small-cell type is modeled to small-cell lung cancer with a regimen consisting of platinum-based chemotherapy and etoposide with variable response. Here, we present a case of poorly differentiated small-cell neuroendocrine tumor originating from the prostate.

Recurrent Mantle Cell Lymphoma Presenting as Gastrointestinal Bleeding.

Mantle cell lymphoma is a rare and aggressive subtype of B-cell non-Hodgkin lymphomas. Mantle cell lymphoma frequently involves extranodal sites, and gastrointestinal tract is involved microscopically and macroscopically in more than 80$ of cases. We present two cases of recurrent mantle cell lymphoma presenting with lower and upper gastrointestinal bleeding, respectively. A 58-year-old woman with a history of recurrent mantle cell lymphoma treated with chemotherapy and stem cell transplantation presented with left-sided abdominal pain and hematochezia. Colonoscopy showed a mass-like lesion in the ascending colon, polyps in the ascending colon, and splenic flexure. A 68-year-old man with a history of mantle cell lymphoma treated with chemotherapy presented with epigastric pain and melena. Esophagogastroduodenoscopy showed a large polypoidal ulcerated mass with oozing in the duodenal bulb. Biopsies in both patients were suggestive of mantle cell lymphoma. Patients with mantle cell lymphoma could be asymptomatic or may present with abdominal pain, obstruction, diarrhea, or gastrointestinal bleeding. In patients presenting with gastrointestinal symptoms, endoscopy must be pursued and biopsies must be taken for any suspicious lesions as well as normal mucosa to exclude mantle cell lymphoma as an etiology for the lesion or symptoms. Even though there are no standard guidelines for endoscopic screening of gastrointestinal tract in asymptomatic patients, one should be aware of involvement of gastrointestinal tract in the early course of disease or recurrent disease. Although mantle cell lymphoma is initially responsive to chemotherapy, it eventually becomes refractory with a median survival of 3-5 years.

Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair: In Vitro and In Vivo Analysis.

INTRODUCTION: Stem cell-based therapies represent a valid approach to restore cardiac function due to their beneficial effect in reducing scar area formation and promoting angiogenesis. However, their translation into the clinic is limited by the poor differentiation and inability to secrete sufficient therapeutic factors. To address this issue, several strategies such as genetic modification and biophysical preconditioning have been used to enhance the efficacy of stem cells for cardiac tissue repair. METHODS: In this study, a biomimetic approach was used to mimic the natural mechanical stimulation of the myocardium tissue. Specifically, human adipose-derived stem cells (hASCs) were cultured on a thin gelatin methacrylamide (GelMA) hydrogel disc and placed on top of a beating cardiomyocyte layer. qPCR studies and metatranscriptomic analysis of hASCs gene expression were investigated to confirm the correlation between mechanical stimuli and cardiomyogenic differentiation. In vivo intramyocardial delivery of pre-conditioned hASCs was carried out to evaluate their efficacy to restore cardiac function in mice hearts post-myocardial infarction. RESULTS: The cyclic strain generated by cardiomyocytes significantly upregulated the expression of both mechanotransduction and cardiomyogenic genes in hASCs as compared to the static control group. The inherent angiogenic secretion profile of hASCs was not hindered by the mechanical stimulation provided by the designed biomimetic system. Finally, in vivo analysis confirmed the regenerative potential of the pre-conditioned hASCs by displaying a significant improvement in cardiac function and enhanced angiogenesis in the peri-infarct region. CONCLUSION: Overall, these findings indicate that cyclic strain provided by the designed biomimetic system is an essential stimulant for hASCs cardiomyogenic differentiation, and therefore can be a potential solution to improve stem-cell based efficacy for cardiovascular repair.

Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue.

The objective of this study was to develop an injectable and biocompatible hydrogel that can deliver a cocktail of therapeutic biomolecules (secretome) secreted by human adipose-derived stem cells (hASCs) to the peri-infarct myocardium. Gelatin and Laponite® were combined to formulate a shear-thinning, nanocomposite hydrogel (nSi Gel) as an injectable carrier of secretome (nSi Gel+). The growth factor composition and the pro-angiogenic activity of the secretome were tested in vitro by evaluating the proliferation, migration and tube formation of human umbilical endothelial cells. The therapeutic efficacy of the nSi Gel + system was then investigated in vivo in rats by intramyocardial injection into the peri-infarct region. Subsequently, the inflammatory response, angiogenesis, scar formation, and heart function were assessed. Biocompatibility of the developed nSi Gel was confirmed by quantitative PCR and immunohistochemical tests which showed no significant differences in the level of inflammatory genes, microRNAs, and cell marker expression compared to the untreated control group. In addition, the only group that showed a significant increase in capillary density, reduction in scar area and improved cardiac function was treated with the nSi Gel+. Our in vitro and in vivo findings demonstrate the potential of this new secretome-loaded hydrogel as an alternative strategy to treat myocardial infarction. STATEMENT OF SIGNIFICANCE: Stem cell based-therapies represent a possible solution to repair damaged myocardial tissue by promoting cardioprotection, angiogenesis, and reduced fibrosis. However, recent evidence indicates that most of the positive outcomes are likely due to the release of paracrine factors (cytokines, growth factors, and exosomes) from the cells and not because of the local engraftment of stem cells. This cocktail of essential growth factors and paracrine signals is known as secretome can be isolated in vitro, and the biomolecule composition can be controlled by varying stem-cell culture conditions. Here, we propose a straightforward strategy to deliver secretome produced from hASCs by using a nanocomposite injectable hydrogel made of gelatin and Laponite®. The designed secretome-loaded hydrogel represents a promising alternative to traditional stem cell therapy for the treatment of acute myocardial infarction.

MicroRNA-210-mediated proliferation, survival, and angiogenesis promote cardiac repair post myocardial infarction in rodents.

An innovative approach for cardiac regeneration following injury is to induce endogenous cardiomyocyte (CM) cell cycle re-entry. In the present study, CMs from adult rat hearts were isolated and transfected with cel-miR-67 (control) and rno-miR-210. A significant increase in CM proliferation and mono-nucleation were observed in miR-210 group, in addition to a reduction in CM size, multi-nucleation, and cell death. When compared to control, ß-catenin and Bcl-2 were upregulated while APC (adenomatous polyposis coli), p16, and caspase-3 were downregulated in miR-210 group. In silico analysis predicted cell cycle inhibitor, APC, as a direct target of miR-210 in rodents. Moreover, compared to control, a significant increase in CM survival and proliferation were observed with siRNA-mediated inhibition of APC. Furthermore, miR-210 overexpressing C57BL/6 mice (210-TG) were used for short-term ischemia/reperfusion study, revealing smaller cell size, increased mono-nucleation, decreased multi-nucleation, and increased CM proliferation in 210-TG hearts in contrast to wild-type (NTG). Likewise, myocardial infarction (MI) was created in adult mice, echocardiography was performed, and the hearts were harvested for immunohistochemistry and molecular studies. Compared to NTG, 210-TG hearts showed a significant increase in CM proliferation, reduced apoptosis, upregulated angiogenesis, reduced infarct size, and overall improvement in cardiac function following MI. ß-catenin, Bcl-2, and VEGF (vascular endothelial growth factor) were upregulated while APC, p16, and caspase-3 were downregulated in 210-TG hearts. Overall, constitutive overexpression of miR-210 rescues heart function following cardiac injury in adult mice via promoting CM proliferation, cell survival, and angiogenesis. KEY MESSAGES: MiRNA-210 transfected adult rat CMs show proliferation and reduced cell death in vitro. Cell cycle inhibitor APC is a target of miR-210. MiR-210 overexpressing (210-TG) mouse hearts show CMs cell cycle re-entry and survival post myocardial injury. 210-TG mice show significant neovascularization and angiogenic potential post myocardial infarction. 210-TG hearts show reduced infarct size following ischemic injury.

MicroRNA-1825 induces proliferation of adult cardiomyocytes and promotes cardiac regeneration post ischemic injury.

In mammals, proliferative capacity of cardiomyocytes is lost soon after birth, while zebrafish and other lower organisms like newts are known to regenerate injured hearts even at an adult age. Here, we show that miR-1825 can induce robust proliferation of adult rat cardiomyocytes and can improve cardiac function in-vivo post myocardial infarction. Rat adult cardiomyocytes transfected with miR-1825 showed a significant increase in DNA synthesis, mitosis, cytokinesis, and an increase in cell number when compared to cel-miR-67 transfected control. We also observed a reduction in mitochondrial number and a decrease in ROS and DNA-damage. RNA-sequencing data identified NDUFA10, a key gene involved in the mitochondrial electron transport chain to be a direct target of miR-1825. SiRNA mediated silencing of NDUFA10 showed a significant increase in cardiomyocyte proliferation indicating its role downstream of miRNA-1825. In addition, microRNA microarray results identified miR-1825 to regulate expression of a known proliferation inducing miRNA, miR-199a. We also identified the direct targets of miR-199a, namely p16, Rb1, and Meis2 to be downregulated following miR-1825 transfection. However, miR-199a alone did not have similar proliferation inducing effects as miR-1825, indicating that miR-1825 works through multiple pathways and is a master regulator of cardiomyocyte proliferation. In addition, our in-vivo analysis in animal models of LAD ligation and intra-cardiac miRNA delivery showed proliferation of endogenous cardiomyocytes in the peri-infarcted region and an improvement in heart function. These findings establish miR-1825 as a potential therapeutic agent for induction of cardiomyocyte proliferation and cardiac regeneration, with a significant translational potential.

Nanodiamond-based injectable hydrogel for sustained growth factor release: Preparation, characterization and in vitro analysis.

Nanodiamonds (NDs) represent an emerging class of carbon nanomaterials that possess favorable physical and chemical properties to be used as multifunctional carriers for a variety of bioactive molecules. Here we report the synthesis and characterization of a new injectable ND-based nanocomposite hydrogel which facilitates a controlled release of therapeutic molecules for regenerative applications. In particular, we have formulated a thermosensitive hydrogel using gelatin, chitosan and NDs that provides a sustained release of exogenous human vascular endothelial growth factor (VEGF) for wound healing applications. Addition of NDs improved the mechanical properties of the injectable hydrogels without affecting its thermosensitive gelation properties. Biocompatibility of the generated hydrogel was verified by in vitro assessment of apoptotic gene expressions and anti-inflammatory interleukin productions. NDs were complexed with VEGF and the inclusion of this complex in the hydrogel network enabled the sustained release of the angiogenic growth factor. These results suggest for the first time that NDs can be used to formulate a biocompatible, thermosensitive and multifunctional hydrogel platform that can function both as a filling agent to modulate hydrogel properties, as well as a delivery platform for the controlled release of bioactive molecules and growth factors. STATEMENT OF SIGNIFICANCE: One of the major drawbacks associated with the use of conventional hydrogels as carriers of growth factors is their inability to control the release kinetics of the loaded molecules. In fact, in most cases, a burst release is inevitable leading to diminished therapeutic effects and unsuccessful therapies. As a potential solution to this issue, we hereby propose a strategy of incorporating ND complexes within an injectable hydrogel matrix. The functional groups on the surface of the NDs can establish interactions with the model growth factor VEGF and promote a prolonged release from the polymer network, therefore, providing a longer therapeutic effect. Our strategy demonstrates the efficacy of using NDs as an essential component for the design of a novel injectable nanocomposite system with improved release capabilities.

Tumors Presenting as Multiple Cranial Nerve Palsies.

Cranial nerve palsy could be one of the presenting features of underlying benign or malignant tumors of the head and neck. The tumor can involve the cranial nerves by local compression, direct infiltration or by paraneoplastic process. Cranial nerve involvement depends on the anatomical course of the cranial nerve and the site of the tumor. Patients may present with single or multiple cranial nerve palsies. Multiple cranial nerve involvement could be sequential or discrete, unilateral or bilateral, painless or painful. The presentation could be acute, subacute or recurrent. Anatomic localization is the first step in the evaluation of these patients. The lesion could be in the brain stem, meninges, base of skull, extracranial or systemic disease itself. We present 3 cases of underlying neoplasms presenting as cranial nerve palsies: a case of glomus tumor presenting as cochlear, glossopharyngeal, vagus and hypoglossal nerve palsies, clivus tumor presenting as abducens nerve palsy, and diffuse large B-cell lymphoma presenting as oculomotor, trochlear, trigeminal and abducens nerve palsies due to paraneoplastic involvement. History and physical examination, imaging, autoantibodies and biopsy if feasible are useful for the diagnosis. Management outcomes depend on the treatment of the underlying tumor.

Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid.

Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass) and a low-grade neuroendocrine neoplasm (carcinoid of rectum). The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa.

Development, Functioning, and Effectiveness of a Preoperative Risk Assessment Clinic.

Lee first described the concept of preoperative assessment testing (PAT) clinic in 1949. An efficiently run clinic is associated with increased cost-effectiveness by lowering preoperative admission time and thus reducing the length of stay and the associated costs. The setup of the PAT clinic should be based on the needs, culture, and resources of the institution. Various models for the setup of PAT clinic have been described, including the concept of a perioperative surgical home, which is a patient-centered model designed to improve health and the delivery of health care and to reduce the cost of care. Although there are several constraints in the development of PAT clinics, with increasing awareness about the usefulness of pre-operative risk assessments, growing bodies of literature, and evidence-based guidelines, these clinics are becoming a medical necessity for the improvement of perioperative care.

Stem cell secretome-rich nanoclay hydrogel: a dual action therapy for cardiovascular regeneration.

A nanocomposite hydrogel with photocrosslinkable micro-porous networks and a nanoclay component was successfully prepared to control the release of growth factor-rich stem cell secretome. The proven pro-angiogenic and cardioprotective potential of this new bioactive system provides a valuable therapeutic platform for cardiac tissue repair and regeneration.

MicroRNAs regulating meis1 expression and inducing cardiomyocyte proliferation.

Cardiovascular disease has been the biggest killer in the United States for decades, with almost a million new cases each year. Even though mammalian rodent neonatal cardiomyocytes show proliferative potential for up to 5 days, adult cardiomyocytes lose this ability. Insufficient cardiomyocyte proliferation is one of the major reasons for the lack of regeneration of myocardial tissue, post injury. Several studies have looked at the mechanisms responsible for the arrest in proliferation at an adult stage. Following up on a recent study by Eulalio et al's study on functional screening of 875 miRNAs for neonatal cardiomyocyte proliferation, we recently identified several miRNAs that induce proliferation in naturally senescent adult cardiomyocytes. Additional studies by Mahmood et al 2013 have identified Meis1 as the major regulator of cardiomyocyte cell cycle. In our present study we have identified three of the adult cardiomyocyte proliferation inducing miRNAs to have binding sites on the 3'UTR of Meis1 gene by in-silico analysis and luciferase assay. Additionally we found these miRNAs; miR-548c-3p, miR-509-3p, and miR-23b-3p to induce significant proliferation in adult cardiomyocytes through translational inhibition of Meis1. We found a significant increase in the number of ACMs with each miRNA, in combination, and with siRNA mediated inhibition of Meis1 gene. We confirmed that these microRNAs, through inhibition of Meis1, affect its downstream targets and thereby regulate cell-cycle progression. Further investigating of the mechanism of action of these miRNAs can identify other treatment options for abnormalities associated with the lack of cardiac regeneration post myocardial injury.

MicroRNAs Inducing Proliferation of Quiescent Adult Cardiomyocytes.

In the United States, each year over 700,000 people suffer from a heart attack and over 25% of deaths are related to heart disease, making it the leading cause of death. Following ischemic injury a part of the heart muscle is replaced by a scar tissue, reducing its functioning capacity. Recent advancements in surgical intervention and pharmacotherapy only provide symptomatic relief and do not address the root cause of the problem which is the massive loss of cardiomyocytes (CM). Therefore, the development of novel therapeutic intervention for the repair and regeneration of ischemic myocardium remains an area of intense research. While existing CM in zebra fish and neonatal mice are known to proliferate and replenish the infarcted heart, it has been shown that adult mammalian CM lose this ability, thus preventing regeneration of the scar tissue. There have been many attempts to facilitate regeneration of ischemic heart but have met with limited success. Micro-RNAs (miRNAs) are one of the promising candidates towards this goal as they are known to play important regulatory roles during differentiation and tissue regeneration, and regulate genetic information by post-transcriptional modification as well as regulation of other miRNAs. While previous work by Eulalio et al., showed miRNAs inducing proliferation in neonatal CM (NCM), we here identify miRNAs inducing proliferation of rat adult-CM (ACM). This commentary while analyses recent work by Eulalio et al[1] also shows some new data with microRNAs in rat adult-CMs. Further work into the mechanism of these miRNAs can determine their therapeutic potential towards regenerating cardiac tissue post ischemic injury.