Evaluation of retinal nerve fiber layer,ganglion cell layer,and optic nerve head morphological parameters in patients with obstructive sleep apnea and comparison with normal population

Purpose:To compare the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and optic nerve head (ONH) morphological parameters between obstructive sleep apnea (OSA) patients and age-matched controls using spectral domain optical coherence tomography (SD-OCT).Methods:This case control study was conducted in a multi-specialty tertiary care hospital from 2014 to 2016. Patients diagnosed to have OSA by overnight polysomnography were included in the study. Fifty eyes of 25 OSA patients with clinically normal optic disc were compared with 50 eyes of age-matched controls. The study population underwent detailed ophthalmological evaluation including SD-OCT.Results:There was significant thinning of the superior, inferior, and average RNFL in the OSA group when compared to controls. GCL analysis also showed a significant thinning of the six sectors as well as average and minimum ganglion cell layer + inner plexiform layer in OSA patients. The optic nerve head rim area was significantly decreased in OSA patients when compared to controls.Conclusion:OSA patients even with clinically normal optic disc showed significant decrease in the RNFL thickness, GCL thickness, and rim area when compared to age-matched controls. Hence, these patients constitute a high-risk population who need to be regularly screened and followed up for ocular co-morbidities.     

First orthotopic liver transplantation in patient with biliary atresia and situs inversus in spain

Biliary atresia is the most common indication for liver transplantation in the pediatric age group. The Kasai portoenterostomy has become established as the primary treatment for biliary atresia. If portoenterostomy fails, death before 2 years of age is likely without liver transplantation. The most common multiple malformation syndrome associated with biliary atresia is polysplenia syndrome, which forms a constellation of defects of body symmetry, splenic development and vascular anomalies, including situs inversus, polysplenia and others. The situs inversus was formerly considered an absolute contraindication for liver transplantation. Recently however, several case reports have been published suggesting that neither situs inversus nor this particular subset of vascular abnormalities should be considered contraindications to liver transplantation. We present one case of liver transplantation performed in patient with biliary atresia, situs inversus and polysplenia. This is the first report described in Spain for a liver transplant in a child with biliary atresia plus situs inversus.     

Intraabdominal adhesion formation after preperitoneal dissection in the murine model

Background: The laparoscopic approach to hernia repair has been advocated by many as a potentially superior method of herniorraphy. Several techniques have been described, each with its own proposed advantages. These techniques involve different anatomic approaches, the most recent of which is the totally extraperitoneal approach (TEPA). One presumed advantage of the extraperitoneal approach is the avoidance of adhesion formation because the peritoneum is not entered and mesh is not placed in direct contact with intra-abdominal structures. We hypothesize, however, that when the peritoneum is dissected from the abdominal wall, it is partially devascularized, leading to scar formation and potential adhesion formation. This would suggest that the TEPA method of herniorraphy may not completely avoid the risks of intra-abdominal adhesion formation. Methods: After appropriate approval was obtained, 88 male Sprague-Dawley rats were divided into two equal groups. One group underwent laparotomy followed by careful blunt dissection of the peritoneum from the left abdominal wall. The control group underwent laparotomy without manipulation of the peritoneum. All animals were re-explored 14 days later, and the abdominal cavity was examined for adhesions. The type and location of any adhesion was recorded. Results: Adhesion formation occurred in 10 of 44 (23%) subjects in the peritoneal dissection group, compared with 3 of 44 (7%) in the nondissection group (p < 0.05). Conclusions: Dissection of the peritoneum from the overlying abdominal wall in the murine model leads to intra-abdominal adhesion formation. This suggests that peritoneal dissection in the TEPA method of herniorraphy may lead to intra-abdominal adhesion formation. Received: 13 January 1998/Accepted: 22 May 1998     

MRI angiography is superior to helical CT for detection of HCC prior to liver transplantation: an explant correlation

Helical computerized tomography (CT) and magnetic resonance imaging (MRI) are used for staging of hepatocellular carcinoma (HCC) prior to curative treatments but underestimate tumor extension in 30% to 50% of cases when compared with pathologic explants. This study compares a new technology, MRI angiography (MRA), with triphasic helical CT in detection of HCC. Fifty cirrhotic patients, 29 with HCC, undergoing liver transplantation were analyzed. MRA was performed with a 3-D breath-hold fast spoiled gradient-echo sequence by using an effective section thickness of 2 to 2.5 mm. The gold standard was the pathologic examination (liver cut into 5-mm slices). One hundred twenty-seven lesions were identified at the explant: 76 HCC, 13 high-grade dysplastic nodules, 31 macroregenerative nodules, 7 hemangiomas. Diameter of the main HCC nodules was 29 +/- 14 mm and 11 +/- 7 mm for the 47 additional nodules. On a per nodule basis, sensitivity of MRA was superior to CT (58/76 [76%] vs. 43/70 [61%], respectively, P =.001). Sensitivity of MRA for detection of additional nodules decreased with size (>20 mm: 6/6 [100%]; 10-20 mm: 16/19 [84%]; <10 mm: 7/22 [32%]) and was superior to CT for nodules 10 to 20 mm (84% vs. 47%, P =.016). Nonspecific hypervascular nodules >5 mm at MRA were HCC in two thirds of the cases. In conclusion, MRA has a high diagnostic accuracy for HCC > or =10 mm and is more sensitive than triphasic helical CT in nodules sized 10 to 20 mm. MRA is the optimal technique for HCC staging prior to curative therapies.     

Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes

OBJECTIVE: Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of growth hormone (GH) and promotes appetite and adiposity. It has also been reported to increase myocardial contractility, induce vasodilation, and protect against myocardial-infarction-induced heart failure. Though principally gastric in origin, it is also produced by other tissues. This work investigated whether cardiomyocytes synthesize and secrete ghrelin, and how its production in these cells responds to stress and exogenous apoptotic agents. METHODS: Ghrelin and its receptor expression was studied by RT-PCR, immunohistochemistry, and competitive binding studies in mouse adult cardiomyocyte cell line HL-1, and primary cultured human cardiomyocytes. Ghrelin accumulation in cardiomyocyte culture medium was measured by radioimmunoassay. Viability and apoptosis assays were carried on by MTT and Hoechst dye vital staining, respectively. RESULTS: RT-PCR showed that HL-1 cells produce mRNAs for both ghrelin and GHS-R, and that GHS-R1a is expressed in human cardiomyocytes; and competitive binding studies using (125)I-labelled ghrelin showed efficient constitutive expression of GHS-R at the surface of HL-1 cells. Immunohistochemistry confirmed the presence of ghrelin in the cytoplasm of HL-1 cells and of isolated human cardiomyocytes in primary culture. Radioimmunoassay showed that ghrelin was secreted by HL-1 cells and human cardiomyocytes into the culture medium. Ghrelin did not modify the viability of HL-1 cells subjected to 12-h starvation, but did protect against the apoptosis inducer cytosine arabinoside (AraC). Finally, production of ghrelin mRNA in HL-1 cardiomyocytes was reduced by AraC but increased if exposure to AraC was preceded by GH treatment. CONCLUSIONS: Ghrelin is synthesized and secreted by isolated murine and human cardiomyocytes, probably with paracrine/autocrine effects, and may be involved in protecting these cells from apoptosis.     

The Role of GJD2(Cx36) in Refractive Error Development

Refractive errors are common eye disorders characterized by a mismatch between the focal power of the eye and its axial length. An increased axial length is a common cause of the refractive error myopia (nearsightedness). The substantial increase in myopia prevalence over the last decades has raised public health concerns because myopia can lead to severe ocular complications later in life. Genomewide association studies (GWAS) have made considerable contributions to the understanding of the genetic architecture of refractive errors. Among the hundreds of genetic variants identified, common variants near the gap junction delta-2 (GJD2) gene have consistently been reported as one of the top hits. GJD2 encodes the connexin 36 (Cx36) protein, which forms gap junction channels and is highly expressed in the neural retina. In this review, we provide current evidence that links GJD2(Cx36) to the development of myopia. We summarize the gap junctional communication in the eye and the specific role of GJD2(Cx36) in retinal processing of visual signals. Finally, we discuss the pathways involving dopamine and gap junction phosphorylation and coupling as potential mechanisms that may explain the role of GJD2(Cx36) in refractive error development.     

Childhood cardiac function after twin-to-twin transfusion syndrome – a 10-year follow up

Aim:  To perform a 10-year follow up of cardiac structure and function after twin-to-twin transfusion syndrome (TTTS) – a severe foetal circulatory complication associated with myocardial hypertrophy in the recipient twin.
Methods:  Cardiac dimensions, systolic and diastolic function as assessed by echocardiography including flow and tissue Doppler velocimetry in 22 healthy survivors of TTTS with a mean age of 9.6 (7.2–11.8) years.
Results:  The donor and recipient twin did not show any differences in end-diastolic ventricular size, interventricular septum thickness, diameter of right ventricular outflow tract, cardiac valves, coronary arteries or in systolic blood flow velocities. However, compared with the donors, the recipients had significantly lower E/A ratios because of lower E-waves in both mitral (−0.15 ± 0.10, p < 0.01) and tricuspid (−0.09 ± 0.07, p < 0.01) valves, indicating reduced early diastolic ventricular fillings compared with donors.
Conclusion:  At school age, twins surviving TTTS had a cardiac structure and function within normal range. There were no differences in heart structure or systolic ventricular function between twins but, compared with the donor twin, we found a reduced early diastolic function in the recipient.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Cells navigate with a local-excitation,global-inhibition-biased excitable network

Cells have an internal compass that enables them to move along shallow chemical gradients. As amoeboid cells migrate, signaling events such as Ras and PI3K activation occur spontaneously on pseudopodia. Uniform stimuli trigger a symmetric response, whereupon cells stop and round up; then localized patches of activity appear as cells spread. Finally cells adapt and resume random migration. In contrast, chemotactic gradients continuously direct signaling events to the front of the cell. Local-excitation, global-inhibition (LEGI) and reaction–diffusion models have captured some of these features of chemotaxing cells, but no system has explained the complex response kinetics, sensitivity to shallow gradients, or the role of recently observed propagating waves within the actin cytoskeleton. We report here that Ras and PI3K activation move in phase with the cytoskeleton events and, drawing on all of these observations, propose the LEGI-biased excitable network hypothesis. We formulate a model that simulates most of the behaviors of chemotactic cells: In the absence of stimulation, there are spontaneous spots of activity. Stimulus increments trigger an initial burst of patches followed by localized secondary events. After a few minutes, the system adapts, again displaying random activity. In gradients, the activity patches are directed continuously and selectively toward the chemoattractant, providing an extraordinary degree of amplification. Importantly, by perturbing model parameters, we generate distinct behaviors consistent with known classes of mutants. Our study brings together heretofore diverse observations on spontaneous cytoskeletal activity, signaling responses to temporal stimuli, and spatial gradient sensing into a unified scheme.     

Antiviral Activity of Ribosome-Inactivating Proteins

Ribosome-inactivating proteins (RIPs) are rRNA N-glycosylases from plants (EC 3.2.2.22) that inactivate ribosomes thus inhibiting protein synthesis. The antiviral properties of RIPs have been investigated for more than four decades. However, interest in these proteins is rising due to the emergence of infectious diseases caused by new viruses and the difficulty in treating viral infections. On the other hand, there is a growing need to control crop diseases without resorting to the use of phytosanitary products which are very harmful to the environment and in this respect, RIPs have been shown as a promising tool that can be used to obtain transgenic plants resistant to viruses. The way in which RIPs exert their antiviral effect continues to be the subject of intense research and several mechanisms of action have been proposed. The purpose of this review is to examine the research studies that deal with this matter, placing special emphasis on the most recent findings.