Self-Directed Learning and the Impact of Leadership: Analyzing Keys for Success from a Covenental Perspective

The current state of education seems to beg for visionary changes to truly impact students and prepare them for the future. Self-directed learning models purport to do just that, by preparing students to be self-motivated, lifelong learners. While many educators seek to apply self-directed practices, research reveals that there are several obstacles that can hinder self-directed learning. Duby’s 2006 study of schools employing self-directed learning investigated how leaders successfully overcome these hindrances via specific leadership attitudes and behaviors that not only effectively overcame these obstacles, but are also reflected in the covenantal perspective of leadership. Using content analysis, this paper further explores the findings of Duby’s study of educational leaders, analyzing them within the covenantal construct developed by Fischer (2003), in order to better understand the relationship between effective leadership practice and the covenantal perspective. This study revealed intriguing similarities between particulars of the CFA model and the leadership practices exhibited in the self-directed learning schools. These similarities also present opportunities for future study, including whether visionary organizations are more apt to be motivated by covenantal principles and examining the type of for-profit organizations that are more apt to embody the tenets of CFA

Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

Attitude shifts and knowledge gains: Evaluating men who have sex with men sensitisation training for healthcare workers in the Western Cape, South Africa

Background: Men who have sex with men (MSM) in South Africa experience discrimination from healthcare workers (HCWs), impeding health service access.Objectives: To evaluate the outcomes of an MSM sensitisation training programme for HCWs implemented in the Western Cape province (South Africa).Methods: A training programme was developed to equip HCWs with the knowledge, awareness and skills required to provide non-discriminatory, non-judgemental and appropriate services to MSM. Overall, 592 HCWs were trained between February 2010 and May 2012. Trainees completed self-administered pre- and post-training questionnaires assessing changes in knowledge. Two-sample t-tests for proportion were used to assess changes in specific answers and the Wilcoxon rank-sum test for overall knowledge scores. Qualitative data came from anonymous post-training evaluation forms completed by all trainees, in combination with four focus group discussions (n = 28) conducted six months after their training.Results: Fourteen per cent of trainees had received previous training to counsel clients around penile–anal intercourse, and 16% had previously received training around sexual health issues affecting MSM. There was a statistically significant improvement in overall knowledge scores (80% – 87%, p < 0.0001), specifically around penile–anal intercourse, substance use and depression after the training. Reductions in negative attitudes towards MSM and increased ability for HCWs to provide non-discriminatory care were reported as a result of the training.Conclusion: MSM sensitisation training for HCWs is an effective intervention to increase awareness on issues pertaining to MSM and how to engage around them, reduce discriminatory attitudes and enable the provision of non-judgemental and appropriate services by HCWs

A procedure for localisation and electrophysiological characterisation of ion channels heterologously expressed in a plant context

BACKGROUND: In silico analyses based on sequence similarities with animal channels have identified a large number of plant genes likely to encode ion channels. The attempts made to characterise such putative plant channels at the functional level have most often relied on electrophysiological analyses in classical expression systems, such as Xenopus oocytes or mammalian cells. In a number of cases, these expression systems have failed so far to provide functional data and one can speculate that using a plant expression system instead of an animal one might provide a more efficient way towards functional characterisation of plant channels, and a more realistic context to investigate regulation of plant channels. RESULTS: With the aim of developing a plant expression system readily amenable to electrophysiological analyses, we optimised experimental conditions for preparation and transformation of tobacco mesophyll protoplasts and engineered expression plasmids, that were designed to allow subcellular localisation and functional characterisation of ion channels eventually in presence of their putative (possibly over-expressed) regulatory partners. Two inward K(+ )channels from the Shaker family were functionally expressed in this system: not only the compliant KAT1 but also the recalcitrant AKT1 channel, which remains electrically silent when expressed in Xenopus oocytes or in mammalian cells. CONCLUSION: The level of endogenous currents in control protoplasts seems compatible with the use of the described experimental procedures for the characterisation of plant ion channels, by studying for instance their subcellular localisation, functional properties, structure-function relationships, interacting partners and regulation, very likely in a more realistic context than the classically used animal systems

Inadequate Sedation During Therapeutic Paralysis: Use of Bispectral Index in Critically Ill Patients

Background: Patients receiving therapeutic paralysis may experience inadequate sedation due to intrinsic limitations of behavioral sedation assessment. Bispectral index (BISTM) provides an objective measure of sedation; however, the role of BISTM is not well defined in intensive care unit (ICU) patients on neuromuscular blocking agents (NMBA). Objective: The aim of this study was to delineate the relationship between BISTM and level of sedation for critically ill patients during therapeutic paralysis. Methods: This was a retrospective observational study conducted in ICU patients receiving continuous infusion NMBA and BISTM monitoring. The primary endpoint was the correlation of BISTM\60 during therapeutic paralysis with a Richmond Agitation Sedation Score (RASS) of -4 to -5 (i.e., deep or unarousable sedation) at the time of emergence from therapeutic paralysis. Results: Thirty-one patients were included in the analysis. Three of these patients (9.6 %) were inadequately sedated upon emergence from paralysis; that is, restless or agitated (RASS ?1 to ?2). We did not observe a correlation between BISTM and RASS upon emergence from paralysis (r = 0.27, p = 0.14). The sensitivity of BISTM\60 in predicting deep sedation (RASS -5 to -4) was 100 % (95 % confidence interval [CI] 0–100) with a positive predictive value of 35.7 %. The sensitivity and positive predictive value of BISTM\60 in predicting light sedation or deeper (RASS -5 to -2) was 92.9 % (95 %CI 83.3–100) and 92.9 %, respectively. Conclusion: These results suggest that 1 in 10 critically ill patients receiving therapeutic paralysis may be inadequately sedated. BISTM monitoring may serve as a useful adjunctive measure of sedation in critically ill patients receiving therapeutic paralysis

Inadequate Sedation During Therapeutic Paralysis: Use of Bispectral Index in Critically Ill Patients

Background Patients receiving therapeutic paralysis may experience inadequate sedation due to intrinsic limitations of behavioral sedation assessment. Bispectral index (BIS™) provides an objective measure of sedation; however, the role of BIS™ is not well defined in intensive care unit (ICU) patients on neuromuscular blocking agents (NMBA). Objective The aim of this study was to delineate the relationship between BIS™ and level of sedation for critically ill patients during therapeutic paralysis. Methods This was a retrospective observational study conducted in ICU patients receiving continuous infusion NMBA and BIS™ monitoring. The primary endpoint was the correlation of BIS™ \u3c 60 during therapeutic paralysis with a Richmond Agitation Sedation Score (RASS) of −4 to −5 (i.e., deep or unarousable sedation) at the time of emergence from therapeutic paralysis. Results Thirty-one patients were included in the analysis. Three of these patients (9.6 %) were inadequately sedated upon emergence from paralysis; that is, restless or agitated (RASS +1 to +2). We did not observe a correlation between BIS™ and RASS upon emergence from paralysis (r = 0.27, p = 0.14). The sensitivity of BIS™ \u3c 60 in predicting deep sedation (RASS −5 to −4) was 100 % (95 % confidence interval [CI] 0–100) with a positive predictive value of 35.7 %. The sensitivity and positive predictive value of BIS™ \u3c 60 in predicting light sedation or deeper (RASS −5 to −2) was 92.9 % (95 %CI 83.3–100) and 92.9 %, respectively. Conclusion These results suggest that 1 in 10 critically ill patients receiving therapeutic paralysis may be inadequately sedated. BIS™ monitoring may serve as a useful adjunctive measure of sedation in critically ill patients receiving therapeutic paralysis

A mouse model for adult cardiac-specific gene deletion with CRISPR/Cas9

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) 9 genomic editing has revolutionized the generation of mutant animals by simplifying the creation of null alleles in virtually any organism. However, most current approaches with this method require zygote injection, making it difficult to assess the adult, tissue-specific functions of genes that are widely expressed or which cause embryonic lethality when mutated. Here, we describe the generation of cardiac-specific Cas9 transgenic mice, which express high levels of Cas9 in the heart, but display no overt defects. In proof-of-concept experiments, we used Adeno-Associated Virus 9 (AAV9) to deliver single-guide RNA (sgRNA) that targets the Myh6 locus exclusively in cardiomyocytes. Intraperitoneal injection of postnatal cardiac-Cas9 transgenic mice with AAV9 encoding sgRNA against Myh6 resulted in robust editing of the Myh6 locus. These mice displayed severe cardiomyopathy and loss of cardiac function, with elevation of several markers of heart failure, confirming the effectiveness of this method of adult cardiac gene deletion. Mice with cardiac-specific expression of Cas9 provide a tool that will allow rapid and accurate deletion of genes following a single injection of AAV9-sgRNAs, thereby circumventing embryonic lethality. This method will be useful for disease modeling and provides a means of rapidly editing genes of interest in the heart

Effects of superovulated heifer diet type and quantity on relative mRNA abundances and pyruvate metabolism in recovered embryos.

This study investigated the effects of quantity and type of diet fed to superovulated donor heifers on molecular and metabolic indices of embryonic development. These effects included the relative abundances of mRNAs for the alpha 1 subunit of Na/K-ATPase and the antioxidant enzyme Cu/Zn-SOD, as well as pyruvate utilization in bovine morulae and blastocysts developed in vivo. Heifers were fed a daily ration of either grass silage and a citrus-beet pulp-based concentrate or grass silage and a barley-based concentrate for 116 days, both at 3 kg per day or ad libitum. In embryos derived from heifers fed the pulp-based diets, the relative abundances of the transcripts were not affected by either day of collection or quantity of diet. In embryos derived from heifers fed the barley-based diets, the relative abundances of the Na/K-ATPase transcripts were also not changed by these main effects, while the relative abundances of the Cu/Zn-SOD transcripts were affected by day of collection and by the quantity of diet. Pyruvate metabolism was affected by day of collection, and was significantly increased in day 8 embryos compared with day 7 and day 6 embryos. Diet quantity did not affect pyruvate utilization, whereas diet type did increase pyruvate metabolism in the barley group when compared with the pulp group. The results of this study show for the first time that molecular and metabolic variations may exist in embryos derived in vivo and developed in donor heifers on nutritional regimens differing in type and quantity. Differences in embryos collected on different developmental days may be attributed to varying cell numbers. Alterations in the relative abundances of the Cu/Zn-SOD transcripts and pyruvate metabolism caused by the quantity of diet fed to the donor animal were likely to have been due to alterations in metabolic end products that accumulate in reproductive tract fluids, whereas differences in embryonic metabolism caused by type of diet are related to the composition of the diet. These findings characterize embryos produced in vivo at the molecular level, indicating that the molecular markers used in the present study can differentiate between populations of embryos produced under different nutritional regimens and determine conditions conductive to the production of good quality embryos

Class I HDAC Inhibition Blocks Cocaine-Induced Plasticity Through Targeted Changes in Histone Methylation

Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the acetylation of histone tails, but little is known about the functional specificity of different HDAC isoforms in the development and maintenance of cocaine-induced plasticity, and prior studies of HDAC inhibitors report conflicting effects on cocaine-elicited behavioral adaptations. Here, we demonstrate that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior, an effect mediated in part via a chromatin-mediated suppression of GABAA receptor subunit expression and inhibitory tone on NAc neurons. Our findings suggest a novel mechanism by which prolonged and selective HDAC inhibition can alter behavioral and molecular adaptations to cocaine and inform the development of novel therapeutics for cocaine addiction

Experiences of Kenyan Healthcare Workers Providing Services to Men Who Have Sex With Men: Qualitative Findings from a Sensitivity Training Programme

Introduction Men who have sex with men (MSM) in Kenya are at high risk for HIV and may experience prejudiced treatment in health settings due to stigma. An on-line computer-facilitated MSM sensitivity programme was conducted to educate healthcare workers (HCWs) about the health issues and needs of MSM patients. Methods Seventy-four HCWs from 49 ART-providing health facilities in the Kenyan Coast were recruited through purposive sampling to undergo a two-day MSM sensitivity training. We conducted eight focus group discussions (FGDs) with programme participants prior to and three months after completing the training programme. Discussions aimed to characterize HCWs’ challenges in serving MSM patients and impacts of programme participation on HCWs’ personal attitudes and professional capacities. Results Before participating in the training programme, HCWs described secondary stigma, lack of professional education about MSM, and personal and social prejudices as barriers to serving MSM clients. After completing the programme, HCWs expressed greater acknowledgement of MSM patients in their clinics, endorsed the need to treat MSM patients with high professional standards and demonstrated sophisticated awareness of the social and behavioural risks for HIV among MSM. Conclusions Findings provide support for this approach to improving health services for MSM patients. Further efforts are needed to broaden the reach of this training in other areas, address identified barriers to HCW participation and evaluate programme effects on patient and HCW outcomes using rigorous methodology