The Epigenetics of Pluripotency in Embryonic Stem Cells

The utilisation of pluripotent cells in regenerative medicine requires the cells to be faithfully maintained in a pluripotent state. One epigenetic feature associated with pluripotency in the embryo is the relative global hypomethylation of cytosine (at CpG dinucleotides, 5meC) that occurs within the nucleus of the inner cell mass and epiblast. It is surprising therefore that the global levels of 5meC in embryonic stem cells (ESCs) propagated under conventional methods are as high as many differentiated somatic cells. Using the newly developed antigen retrieval method that incorporates both acid and trypsin based epitope retrieval processes this project assessed the effects of culture conditions on global levels and localization of 5meC in ESCs. The study shows that the loss of global DNA methylation accompanied increased pluripotency achieved by ESC in 2i media or in suspension culture of EBs. It shows for the first time that this was accompanied by the recruitment of 5meC to heterochromatin. It also showed that global hypermethylation is an early response to conditions that favour the loss of pluripotency, and occurs before evidence of the loss pluripotency or morphological differentiation. This finding provides a new framework for further investigation of the epigenetic requirements of the pluripotent state

Physiotherapist-patient communication in entry-level physiotherapy education: a national survey in Nigeria

Background: Clinical communication impacts on physiotherapy treatment outcome and its competence warrants being assessed during training for physiotherapists given the increasing need to improve patient outcomes. Objective: This study aimed to investigate the assessment of clinical communication in entry-level physiotherapy programs in Nigeria. Methods: In a cross-sectional survey, questionnaires were sent by e-mail or hand-delivered to the heads of physiotherapy programs, asking them to consult with faculty members involved in the assessment of clinical communication in undergraduate education. Results: Six of seven physiotherapy programs responded (an 86% response rate). Assessment of clinical communication and methods of assessing clinical communication by the programs showed wide variation. There was an average of two assessments per year. The objective structured clinical examination with patients (21; 38%) and written communications (report/chart) (13; 23%) were the most commonly used assessment methods. Perceived challenges included a lack of facilities, validity, inexperienced examiners, and difficulties in integrating processes and content. Conclusion: A variety of assessment methods are being used in entry-level physiotherapy programs in Nigeria, which target different components of clinical communication skills acquisition. More effort is needed to improve limited facilities and human resources training to enhance clinical communication assessment in Nigerian physiotherapy programs

Antonini Politii siculi panormitani ... De quinta essentia solutiu atque breui epylogo componendorum medicamentorum, cum aliquibus phylosophiae ac medicinae problematibus : libri duo ..

Sign.: A-Z4, 2A-2C4Port. con escudo xil. del Duque de Osun

Discovery of novel plasma biomarker ratios to discriminate traumatic brain injury

Background: Traumatic brain injury (TBI) is a major cause of death and disability. Despite increased awareness, reliable biomarkers are urgently needed to aid in all forms of traumatic brain injury diagnosis and prognosis. Methods: Here, we aim to assess the diagnostic utility of known and novel TBI biomarkers in a pilot patient cohort of severe TBI (sTBI) patients and healthy controls. We analyzed concentrations of S100 calcium binding protein B (S100B), neuron specific enolase (NSE), human kallikrein 6 (hK6) and prostaglandin D2 synthase (PGDS) using ELISA immunoassays. Results: Plasma levels of hK6 and PGDS were significantly lower in sTBI compared with controls, while S100B and NSE were significantly higher. Furthermore, we show that ratios of NSE and S100B with hK6 and PGDS may be able to determine the presence of sTBI better than single markers alone. Conclusions: The findings presented here represent a starting point for future validation, where biomarker ratios can be tested in independent TBI cohorts

Effects of different heel heights on selected gait parameters of young undergraduate females

The objective of this study was to determine the effects of different heel heights on selected gait parameters in a sample of young Nigerian females. A purposive sample of eighty apparently healthy undergraduates of Nnamdi Azikiwe University, Nnewi Campus participated in the study. Their mean age, height, and weight were 21.98± 1.83 years, 1.65±0.06 meters, 59.50±9.34 kilograms respectively. An ex post facto design was used to investigate the effect of different heel heights (3.2cm, 7.8cm and 11.0cm) on selected gait parameters. This was done using a prepared protocol and measurement of gait parameters were taken with a tape rule and stop watch respectively. One-way ANOVA was used to compare differences across the groups. Level of significance was set at 0.05. There were significant differences in mean values of selected gait parameters across the different heel heights for stride length, step length, stride width, cadence, and velocity respectively. However, with post hoc test, no significant difference exist in mean values between bare foot and low heel of all selected parameters for stride length, step length, and cadence respectively, barefoot and mid heel (p=0.142), and mid and high heel for stride width (p= 0.162) respectively. There was a significant difference exists only between low and high heel on velocity. As heel height increases, gait parameters such as stride length and step length shorten while the cadence increases and the stride width widens. It is recommended that to maintain comfort and reduce the adverse side effects associated with wearing the different heel height, women are advised to minimize putting on heeled shoes particularly the mid and high heels

Probiotics supplementation or probiotic-fortified products on sarcopenic indices in older adults: systematic review and meta-analysis from recent randomized controlled trials

Introduction: A noteworthy correlation was seen between changes in the gut microbiome and sarcopenia in older adults. Along with increasing research on probiotic supplementation for various medical problems, we aimed to obtain evidence and summarize the effect of probiotic supplementation on sarcopenic indices among older adults.Methods: We utilized PubMed, EBSCO, and Proquest, in addition to manual search using synonyms and variation for ‘probiotic,’ ‘sarcopenia,’ and ‘older adults.’ Randomized controlled trials investigated the utilization of probiotics or probiotic-containing products in older adults with sarcopenic indices including muscle mass and strength. The random-effects model was applied to the meta-analysis process.Results: Seven studies were obtained with 733 pooled older adults. Probiotic supplementation resulted in a significant increase of muscle mass with adjusted SMD (Standardized Mean Difference) of 0.962 (95% CI: 0.288 to 1.635, p = 0.049) using till and trim analysis and muscle strength with SMD of 1.037 (95% CI: 0.077 to 1.996, p = 0.03). However, both outcomes were associated with significantly high heterogeneity (I2 = 89.5% and I2 = 89.9%, respectively).Conclusion: When opposed to a placebo, the probiotic treatment improved the amount of muscle and its endurance based on recent evidence, however, further studies should be done with larger samples and targeted populations

Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9

Abstract Background The identification of new serum biomarkers with high sensitivity and specificity is an important priority in pancreatic cancer research. Through an extensive proteomics analysis of pancreatic cancer cell lines and pancreatic juice, we previously generated a list of candidate pancreatic cancer biomarkers. The present study details further validation of four of our previously identified candidates: regenerating islet-derived 1 beta (REG1B), syncollin (SYCN), anterior gradient homolog 2 protein (AGR2), and lysyl oxidase-like 2 (LOXL2). Methods The candidate biomarkers were validated using enzyme-linked immunosorbent assays in two sample sets of serum/plasma comprising a total of 432 samples (Sample Set A: pancreatic ductal adenocarcinoma (PDAC, n = 100), healthy (n = 92); Sample Set B: PDAC (n = 82), benign (n = 41), disease-free (n = 47), other cancers (n = 70)). Biomarker performance in distinguishing PDAC from each control group was assessed individually in the two sample sets. Subsequently, multiparametric modeling was applied to assess the ability of all possible two and three marker panels in distinguishing PDAC from disease-free controls. The models were generated using sample set B, and then validated in Sample Set A. Results Individually, all markers were significantly elevated in PDAC compared to healthy controls in at least one sample set (p ≤ 0.01). SYCN, REG1B and AGR2 were also significantly elevated in PDAC compared to benign controls (p ≤ 0.01), and AGR2 was significantly elevated in PDAC compared to other cancers (p \u3c 0.01). CA19.9 was also assessed. Individually, CA19.9 showed the greatest area under the curve (AUC) in receiver operating characteristic (ROC) analysis when compared to the tested candidates; however when analyzed in combination, three panels (CA19.9 + REG1B (AUC of 0.88), CA19.9 + SYCN + REG1B (AUC of 0.87) and CA19.9 + AGR2 + REG1B (AUC of 0.87)) showed an AUC that was significantly greater (p \u3c 0.05) than that of CA19.9 alone (AUC of 0.82). In a comparison of early-stage (Stage I-II) PDAC to disease free controls, the combination of SYCN + REG1B + CA19.9 showed the greatest AUC in both sample sets, (AUC of 0.87 and 0.92 in Sets A and B, respectively). Conclusions Additional serum biomarkers, particularly SYCN and REG1B, when combined with CA19.9, show promise as improved diagnostic indicators of pancreatic cancer, which therefore warrants further validation

Expression and Functional Characterization of the Cancer-related Serine Protease, Human Tissue Kallikrein 14

Human tissue kallikrein 14 (KLK14) is a novel extracellular serine protease. Clinical data link KLK14 expression to several diseases, primarily cancer; however, little is known of its (patho)-physiological role. To functionally characterize KLK14, we expressed and purified recombinant KLK14 in mature and proenzyme forms and determined its expression pattern, specificity, regulation, and in vitro substrates. By using our novel immunoassay, the normal and/or diseased skin, breast, prostate, and ovary contained the highest concentration of KLK14. Serum KLK14 levels were significantly elevated in prostate cancer patients compared with healthy males. KLK14 displayed trypsin-like specificity with high selectivity for P1-Arg over Lys. KLK14 activity could be regulated as follows: 1) by autolytic cleavage leading to enzymatic inactivation; 2) by the inhibitory serpins alpha1-antitrypsin, alpha2-antiplasmin, antithrombin III, and alpha1-antichymotrypsin with second order rate constants (k(+2)/Ki) of 49.8, 23.8, 1.48, and 0.224 microM(-1) min(-1), respectively, as well as plasminogen activator inhibitor-1; and 3) by citrate and zinc ions, which exerted stimulatory and inhibitory effects on KLK14 activity, respectively. We also expanded the in vitro target repertoire of KLK14 to include collagens I-IV, fibronectin, laminin, kininogen, fibrinogen, plasminogen, vitronectin, and insulin-like growth factor-binding proteins 2 and 3. Our results indicate that KLK14 may be implicated in several facets of tumor progression, including growth, invasion, and angiogenesis, as well as in arthritic disease via deterioration of cartilage. These findings may have clinical implications for the management of cancer and other disorders in which KLK14 activity is elevated