Osteogenic potential of human adipose derived stem cell co-culture with human osteoblast on titanium dioxide nanofibrous surface

The study aims to evaluate the osteogenic potential of human adipose derived stem cell (HADSC) co-culture with human osteoblast (HOB) using selected HADSC/HOB ratio of 2:1, 1:1 and 1:2, respectively. The HADSC/HOB was seeded on Titanium dioxide (TiO2) coated with or without nanofibre substrate. The non-coated TiO2 was used as control. The effects of TiO2 based scaffolds on cell adhesion were characterized by scanning electron microscopy (SEM). Cell viability, differentiation and mineralization were assessed by Alamar Blue, alkaline phosphatase (ALP) and Alizarin Red assays, respectively. The combination of HADSC/HOB, 2:1 ratio, seeded on nanofibrous-coated TiO2 showed better cell adhesion, viability, differentiation and mineralization than the other groups. This study offers opportunity to assess in vitro cellular development of HADSC through direct cell to cell contact with HOB. This study indicates that the co-cultured HADSC/HOB seeded on TiO2 based scaffolds may serve as a promising approach to facilitate osteogenic differentiation activity

The apolipoprotein A-I mimetic peptide, ETC-642, reduces chronic vascular inflammation in the rabbit

<p>Abstract</p> <p>Background</p> <p>High-density lipoproteins (HDL) and their main apolipoprotein, apoA-I, exhibit anti-inflammatory properties. The development of peptides that mimic HDL apolipoproteins offers a promising strategy to reduce inflammatory disease. This study aimed to compare the anti-inflammatory effects of ETC-642, an apoA-I mimetic peptide, with that of discoidal reconstituted HDL (rHDL), consisting of full-length apoA-I complexed with phosphatidylcholine, in rabbits with chronic vascular inflammation.</p> <p>Results</p> <p>New Zealand White rabbits (n = 10/group) were placed on chow supplemented with 0.2% (w/w) cholesterol for 6-weeks. The animals received two infusions of saline, rHDL (8 mg/kg apoA-I) or ETC-642 (30 mg/kg peptide) on the third and fifth days of the final week. The infusions of rHDL and ETC-642 were able to significantly reduce cholesterol-induced expression of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the thoracic aorta (p < 0.05). When isolated rabbit HDL was pre-incubated with human coronary artery endothelial cells (HCAECs), prior to stimulation with TNF-α, it was found that HDL from ETC-642 treated rabbits were more effective at inhibiting the TNF-α-induced increase in ICAM-1, VCAM-1 and p65 than HDL isolated from saline treated rabbits (p < 0.05). There were, however, no changes in HDL lipid composition between treatment groups.</p> <p>Conclusions</p> <p>Infusion of ETC-642 causes anti-inflammatory effects that are comparable to rHDL in an animal model of chronic vascular inflammation and highlights that apoA-I mimetic peptides present a viable strategy for the treatment of inflammatory disease.</p

Case report: A giant hemorrhagic adrenocortical carcinoma causing cardiorespiratory embarrassment

Adrenocortical carcinoma (ACC) is a rare aggressive tumor that can be hormone or non-hormone secreting. It is usually associated with fatal outcomes due to its physiological hormonal interaction. We report a successful anaesthetic and surgical management for a patient who presented to us with a huge hemorrhagic ACC which was complicated with acute respiratory failure. A 56-year-old lady presented to us with progressive abdominal distension and right hypochondriac pain for two months. She was anemic with elevated liver enzymes. Urgent computed tomography (CT) of the abdomen and pelvis showed a huge right supra renal mass. She subsequently developed respiratory failure due to splinting of diaphragm, of which successfully underwent an emergency exploratory laparotomy. Subsequent endocrine and histopathological work up showed an adrenocortical carcinoma (ACC). Suprarenal masses usually originate from the adrenal glands. They should be investigated to rule out phaeochromocytoma, which originate from the inner adrenal medulla or outer cortex to form ACC. The latter usually occur in women and of poor prognosis. Huge ACC may cause acute respiratory failure by way of splinting of diaphragm. Both anaesthetic and surgical teams should be well trained in handling patients who undergo adrenal surgeries. A giant hemorrhagic functional ACC is extremely uncommon with very poor prognosis. Such conditions should be investigated to rule out phaeochromocytoma. Its potential neuro-hormonal interactions and anatomical correlations can cause fatal perioperative cardio-respiratory embarrassment. The anaesthetic and surgical teams should be capable in managing the hemodynamic instabilities that may present during surgical manipulation and resection of a large ACC

A collection of open problems in celebration of Imre Leader's 60th birthday

One of the great pleasures of working with Imre Leader is to experience his infectious delight on encountering a compelling combinatorial problem. This collection of open problems in combinatorics has been put together by a subset of his former PhD students and students-of-students for the occasion of his 60th birthday. All of the contributors have been influenced (directly or indirectly) by Imre: his personality, enthusiasm and his approach to mathematics. The problems included cover many of the areas of combinatorial mathematics that Imre is most associated with: including extremal problems on graphs, set systems and permutations, and Ramsey theory. This is a personal selection of problems which we find intriguing and deserving of being better known. It is not intended to be systematic, or to consist of the most significant or difficult questions in any area. Rather, our main aim is to celebrate Imre and his mathematics and to hope that these problems will make him smile. We also hope this collection will be a useful resource for researchers in combinatorics and will stimulate some enjoyable collaborations and beautiful mathematics

Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation

10.1073/pnas.1111628109Proceedings of the National Academy of Sciences1093841-84

MS4A1 Dysregulation in Asbestos-Related Lung Squamous Cell Carcinoma Is Due to CD20 Stromal Lymphocyte Expression

Asbestos-related lung cancer accounts for 4–12% of lung cancers worldwide. We have previously identified ADAM28 as a putative oncogene involved in asbestos-related lung adenocarcinoma (ARLC-AC). We hypothesised that similarly gene expression profiling of asbestos-related lung squamous cell carcinomas (ARLC-SCC) may identify candidate oncogenes for ARLC-SCC. We undertook a microarray gene expression study in 56 subjects; 26 ARLC-SCC (defined as lung asbestos body (AB) counts >20AB/gram wet weight (gww) and 30 non-asbestos related lung squamous cell carcinoma (NARLC-SCC; no detectable lung asbestos bodies; 0AB/gww). Microarray and bioinformatics analysis identified six candidate genes differentially expressed between ARLC-SCC and NARLC-SCC based on statistical significance (p<0.001) and fold change (FC) of >2-fold. Two genes MS4A1 and CARD18, were technically replicated by qRT-PCR and showed consistent directional changes. As we also found MS4A1 to be overexpressed in ARLC-ACs, we selected this gene for biological validation in independent test sets (one internal, and one external dataset (2 primary tumor sets)). MS4A1 RNA expression dysregulation was validated in the external dataset but not in our internal dataset, likely due to the small sample size in the test set as immunohistochemical (IHC) staining for MS4A1 (CD20) showed that protein expression localized predominantly to stromal lymphocytes rather than tumor cells in ARLC-SCC. We conclude that differential expression of MS4A1 in this comparative gene expression study of ARLC-SCC versus NARLC-SCC is a stromal signal of uncertain significance, and an example of the rationale for tumor cell enrichment in preparation for gene expression studies where the aim is to identify markers of particular tumor phenotypes. Finally, our study failed to identify any strong gene candidates whose expression serves as a marker of asbestos etiology. Future research is required to determine the role of stromal lymphocyte MS4A1 dysregulation in pulmonary SCCs caused by asbestos

Impact of Cigarette Smoke Exposure on Innate Immunity: A Caenorhabditis elegans Model

BACKGROUND: Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD) and lung cancer. Respiratory bacterial infections have been shown to be involved in the development of COPD along with impaired airway innate immunity. METHODOLOGY/PRINCIPAL FINDINGS: To address the in vivo impact of cigarette smoke (CS) exclusively on host innate defense mechanisms, we took advantage of Caenorhabditis elegans (C. elegans), which has an innate immune system but lacks adaptive immune function. Pseudomonas aeruginosa (PA) clearance from intestines of C. elegans was dampened by CS. Microarray analysis identified 6 candidate genes with a 2-fold or greater reduction after CS exposure, that have a human orthologue, and that may participate in innate immunity. To confirm a role of CS-down-regulated genes in the innate immune response to PA, RNA interference (RNAi) by feeding was carried out in C. elegans to inhibit the gene of interest, followed by PA infection to determine if the gene affected innate immunity. Inhibition of lbp-7, which encodes a lipid binding protein, resulted in increased levels of intestinal PA. Primary human bronchial epithelial cells were shown to express mRNA of human Fatty Acid Binding Protein 5 (FABP-5), the human orthologue of lpb-7. Interestingly, FABP-5 mRNA levels from human smokers with COPD were significantly lower (p = 0.036) than those from smokers without COPD. Furthermore, FABP-5 mRNA levels were up-regulated (7-fold) after bacterial (i.e., Mycoplasma pneumoniae) infection in primary human bronchial epithelial cell culture (air-liquid interface culture). CONCLUSIONS: Our results suggest that the C. elegans model offers a novel in vivo approach to specifically study innate immune deficiencies resulting from exposure to cigarette smoke, and that results from the nematode may provide insight into human airway epithelial cell biology and cigarette smoke exposure

It's time for a minimum synoptic operation template in patients undergoing laparoscopic cholecystectomy : a systematic review

Background Despite the call to enhance accuracy and value of operation records few international recommended minimal standards for operative notes documentation have been described. This study undertook a systematic review of existing operative reporting systems for laparoscopic cholecystectomy (LC) to fashion a comprehensive, synoptic operative reporting template for the future. Methods A search for all relevant articles was conducted using PubMed version of Medline, Scopus and Web of Science databases in June 2021, for publications from January 1st 2011 to October 25th 2021, using the keywords: laparoscopic cholecystectomy AND operation notes OR operative notes OR proforma OR documentation OR report OR narrative OR audio-visual OR synoptic OR digital. Two reviewers (NOC, GMC) independently assessed each published study using a MINORS score of >= 16 for comparative and >= 10 for non-comparative for inclusion. This systematic review followed PRISMA guidelines and was registered with PROSPERO. Synoptic operative templates from published data were assimilated into one "ideal" laparoscopic operative report template following international input from the World Society of Emergency Surgery board. Results A total of 3567 articles were reviewed. Following MINORS grading 25 studies were selected spanning 14 countries and 4 continents. Twenty-two studies were prospective. A holistic overview of the operative procedure documentation was reported in 6/25 studies and a further 19 papers dealt with selective surgical aspects of LC. A unique synoptic LC operative reporting template was developed and translated into Chinese/Mandarin, French and Arabic. Conclusion This systematic review identified a paucity of publications dealing with operative reporting of LC. The proposed new template may be integrated digitally with hospitals' medical systems and include additional narrative text and audio-visual data. The template may help define new OR (operating room) recording standards and impact on care for patients undergoing LC.Peer reviewe

Robotic surgery in emergency setting : 2021 WSES position paper

Background Robotics represents the most technologically advanced approach in minimally invasive surgery (MIS). Its application in general surgery has increased progressively, with some early experience reported in emergency settings. The present position paper, supported by the World Society of Emergency Surgery (WSES), aims to provide a systematic review of the literature to develop consensus statements about the potential use of robotics in emergency general surgery. Methods This position paper was conducted according to the WSES methodology. A steering committee was constituted to draft the position paper according to the literature review. An international expert panel then critically revised the manuscript. Each statement was voted through a web survey to reach a consensus. Results Ten studies (3 case reports, 3 case series, and 4 retrospective comparative cohort studies) have been published regarding the applications of robotics for emergency general surgery procedures. Due to the paucity and overall low quality of evidence, 6 statements are proposed as expert opinions. In general, the experts claim for a strict patient selection while approaching emergent general surgery procedures with robotics, eventually considering it for hemodynamically stable patients only. An emergency setting should not be seen as an absolute contraindication for robotic surgery if an adequate training of the operating surgical team is available. In such conditions, robotic surgery can be considered safe, feasible, and associated with surgical outcomes related to an MIS approach. However, there are some concerns regarding the adoption of robotic surgery for emergency surgeries associated with the following: (i) the availability and accessibility of the robotic platform for emergency units and during night shifts, (ii) expected longer operative times, and (iii) increased costs. Further research is necessary to investigate the role of robotic surgery in emergency settings and to explore the possibility of performing telementoring and telesurgery, which are particularly valuable in emergency situations. Conclusions Many hospitals are currently equipped with a robotic surgical platform which needs to be implemented efficiently. The role of robotic surgery for emergency procedures remains under investigation. However, its use is expanding with a careful assessment of costs and timeliness of operations. The proposed statements should be seen as a preliminary guide for the surgical community stressing the need for reevaluation and update processes as evidence expands in the relevant literature.Peer reviewe