Hypoxic Culture Conditions as a Solution for Mesenchymal Stem Cell Based Regenerative Therapy

Cell-based regenerative therapies, based on in vitro propagation of stem cells, offer tremendous hope to many individuals suffering from degenerative diseases that were previously deemed untreatable. Due to the self-renewal capacity, multilineage potential, and immunosuppressive property, mesenchymal stem cells (MSCs) are considered as an attractive source of stem cells for regenerative therapies. However, poor growth kinetics, early senescence, and genetic instability during in vitro expansion and poor engraftment after transplantation are considered to be among the major disadvantages of MSC-based regenerative therapies. A number of complex inter-and intracellular interactive signaling systems control growth, multiplication, and differentiation of MSCs in their niche. Common laboratory conditions for stem cell culture involve ambient O-2 concentration (20%) in contrast to their niche where they usually reside in 2-9% O-2. Notably, O-2 plays an important role in maintaining stem cell fate in terms of proliferation and differentiation, by regulating hypoxia-inducible factor-1 (HIF-1) mediated expression of different genes. This paper aims to describe and compare the role of normoxia (20% O-2) and hypoxia (2-9% O-2) on the biology of MSCs. Finally it is concluded that a hypoxic environment can greatly improve growth kinetics, genetic stability, and expression of chemokine receptors during in vitro expansion and eventually can increase efficiency of MSC-based regenerative therapies.Article Link: http://www.hindawi.com/journals/tswj/2013/632972

Soft skills and dental education

Soft skills and hard skills are essential in the practice of dentistry. While hard skills deal with technical proficiency, soft skills relate to a personal values and interpersonal skills that determine a person's ability to fit in a particular situation. These skills contribute to the success of organisations that deal face-to-face with clients. Effective soft skills benefit the dental practice. However, the teaching of soft skills remains a challenge to dental schools. This paper discusses the different soft skills, how they are taught and assessed and the issues that need to be addressed in their teaching and assessment. The use of the module by the Faculty of Dentistry, University of Malaya for development of soft skills for institutions of higher learning introduced by the Ministry of Higher Education, Malaysia.Article Link: http://onlinelibrary.wiley.com/doi/10.1111/eje.12017/abstrac

Finite element analysis of an automated rapid maxillary expander (ARME)

An Automated Rapid Maxillary Expander (ARME), is a specially designed orthodontic appliance to overcome the shortcomings imposed by the traditional butterfly expansion appliance. It operates by automatically widening the maxilla (upper jaw) by expanding the midpalatal suture [1]. This procedure is not feasible after late teenage years due to more rigid facial skeleton features. According to the study by Cozzani [2], the activation of the device could produce 0.25 mm of expansion per day. Over the period of 2 weeks, the expansion produced is up to 7 mm in total [1]. For this study, we explored the mechanism involved in the ARME appliance by using Finite Element Modeling method

Adjunctive buccal and palatal corticotomy for adult maxillary expansion in an animal model

Objective: This study aimed to explore the usefulness of adjunctive buccal and palatal corticotomy for adult maxillary expansion in an animal model using cone-beam computed tomography (CBCT). Methods: Twelve adult sheep were randomly divided into two groups (each n = 6): a control group, where no treatment was administered, and a treatment group, where buccal and palatal corticotomy-assisted maxillary expansion was performed. CBCT scans were taken before (T1) and after (T2) treatment. Differences in all transverse dental and alveolar dimensions, alveolar width at crest level, hard palate level, horizontal bone loss, interdental cusp width and inter-root apex were assessed using Wilcoxon signed-rank and Mann-Whitney U-tests. Kruskal-Wallis tests and pairwise comparisons were used to detect the significance of differences among the inter-premolar and inter-molar widths. Results: CBCT data revealed significant changes in all transverse dental and alveolar dimensions. The mean interpremolar alveolar width showed an increase of 2.29 to 3.62 mm at the hard palate level, 3.89 to 4.38 mm at the alveolar crest level, and 9.17 to 10.42 mm at the buccal cusp level. Dental changes in the vertical dimension were not significant. Conclusions: Our findings based on an adult animal model suggest that adjunctive buccal and palatal corticotomy can allow for both skeletal and dental expansion, with the amount of dental expansion exceeding that of skeletal expansion at alveolar crest and hard palate levels by two and three folds, respectively. Therefore, this treatment modality is potential to enhance the outcomes of maxillary expansion in adults

Feed formulation based on local feed resources and its effects on nutritional-related blood profile in breeder goats

A comparative study was conducted to determine the nutrient composition of different feed formulations and its effect on nutritional related blood profile in breeder goats. Eighteen female adult goats, Capra aegagrus hircus (Boer cross) were selected and allocated into three different groups (n = 6) and assigned according to different feed formulations. Blood sampling was conducted before and after fourth weeks of feeding trial and analysed for selected parameters. Proximate analysis of diets was done and revealed comparable value of crude protein and crude fat. Glucose, total protein and calcium level in serum showed significant difference between groups (P-value 0.05). Fatty acid analysis of feed and serum showed polyunsaturated fatty acid was higher than satureated fatty acid. Overall, diet 3 shows the highest value of all blood parameters analysed in this study. Hence, it is very important to provide animal with nutrient according to production stages as sufficent protein and energy will improve the animal performance in terms breeding efficacy and quality of animal products. This study indicates that different feed formulation affects certain nutritional related blood profile in goat

Tips for writing a case report for the novice author

A case report is a description of important scientific observations that are missed or undetectable in clinical trials. This includes a rare or unusual clinical condition, a previously unreported or unrecognized disease, unusual side effects to therapy or response to treatment, and unique use of imaging modalities or diagnostic tests to assist diagnosis of a disease. Generally, a case report should be short and focussed, with its main components being the abstract, introduction, case description, and discussion. This article discusses the essential components of a case report, with the aim of providing guidelines and tips to novice authors to improve their writing skills

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402