Characteristics of Oligonucleotide Uptake in Human Keratinocyte Cultures

Oligodeoxyribonucleotides have the potential to interfere selectivity with cellular protein synthesis by sequence-specific hybridization to DNA or RNA molecules. We have, investigated the properties of uptake and intracellular localization of fluorescently labeled oligonucleotides in cultured human keratinocytes using confocal laser scanning microscopy. Unlike many other cell types studied, keratinocytes can internalize oligonucleotides without apparent sequestration in endosomes or cell surface accumulation. Uptake is primarily nuclear and unaltered by sodium azide, monensin, or chloroquin pretreatment. We have verified our results with two different fluorophores, fluorescein and Bodipy, and found similar uptake and distribution patterns in both live and fixed cell populations. Surprisingly, we have found uptake to be heterogeneous within a population, with 15-30% of cells internalizing the oligonucleotides. This percentage is drastically increased to roughly 80% at cell population margins, and after release from M phase arrest. These results on uptake and intracellular localization suggest that keratinocytes may have increased sensitivity as target cells for oligonucleotide based gene regulation strategies

Attrition in School Rowing in New Zealand: A Qualitative Descriptive Study

It is widely acknowledged that involvement in sport has positive physical and psychosocial benefits for adolescents. However, concerns have been expressed, both in New Zealand and internationally, about the relatively high attrition rates in youth sport. This qualitative study captured the experiences of eight (five male, three female) adolescents who were no longer participating in high school rowing programs in New Zealand. Data were gathered through semi-structured interviews, and we conducted an inductive thematic analysis. A secondary analysis was then conducted using a self-determination and basic psychological needs framework that placed specific emphasis on need satisfaction and need thwarting. Key findings from this study suggest that participants’ experiences of rowing were initially positive but were subsequently influenced by dissatisfaction and thwarting of basic psychological needs. The findings confirm the significance of coaches and parents providing an environment that supports young athletes’ needs for relatedness. Concerns are also raised about the potentially damaging effects of weight-restricted sport for adolescents. By drawing upon athlete voice, it is hoped that the findings of this study can inform coach education and result in the development of more athlete-supportive rowing programs for adolescent athletes

Cross-Sectional Survey of Perceived Barriers Among Community Pharmacists Who Do Not Immunize, in Wayne County, Michigan

Introduction: The goal of the study was to identify perceived barriers to implementation of vaccination services encountered by independent and small-chain community pharmacies in an urban setting. Methods: Pharmacists in independent and small-chain pharmacies located in 29 Michigan ZIP codes were visited and asked to complete a 5- to 10-min semi-structured interview. Results: A total of 93 independent and 12 small-chain pharmacies participated (n = 105; 61%). The pharmacies filled an average of 700 prescriptions each week with 1.1 pharmacist full-time equivalents and 57 h of technician time. The most common services that participating pharmacies provided were dispensing outpatient medication (99%), medication therapy management (MTM, 65.7%), disease management or coaching (54.3%), point-of-care testing (34.3%), and dispensing medications to inpatient facilities (16.2%). Only seven pharmacies (6.7%) administered vaccinations. When pharmacists were asked to identify what it would take to start to administer vaccines, the most common responses were increased demand from patients (37.1%), adequate time (19%), appropriate space (17.1%), appropriate amount of staff (14.3%), change in attitudes or beliefs of the owner or pharmacists at that pharmacy (13.3%), increased profit related to vaccines (11.4%), and increased awareness among patients about the importance of vaccines (11.4%). The majority of pharmacies (65.3%) reported that only one factor would need to change to start to administer vaccines. Conclusion: Independent and small-chain community pharmacies in an urban, primarily low-income area identified several barriers that have prevented implementation of vaccination services. However, the majority of pharmacies reported that only one factor would need to change in order to begin to administer vaccines. Interventional efforts necessary to address commonly cited barriers may include providing education to pharmacists about the need for community pharmacy-based immunization programs in addition to services provided by physician offices, as well as the importance of proactively providing immunization-related recommendations to patients

Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota

Iron deficiency anaemia (IDA) is a worldwide healthcare problem affecting approximately 25% of the global population. The most common IDA treatment is oral iron supplementation, which has been associated with gastrointestinal (GI) side effects such as constipation and bloating. These can result in treatment non-adherence and the persistence of IDA. Intravenous iron does not cause GI side effects, which may be due to the lack of exposure to the intestinal lumen. Luminal iron can cause changes to the gut microbiota, aiding the promotion of pathogenic species and decreasing beneficial protective species. Iron is vital for methanogenic archaea, which rely on iron for growth and metabolism. Increased intestinal methane has been associated with slowing of intestinal transit, constipation, and bloating. Here we explore the literature to understand a potential link between iron and methanogenesis as a novel way to understand the mechanism of oral iron supplementation induced GI side effects

Investigating the Solubility and Cytocompatibility of CaO-Na2O-SiO2/TiO2 Bioactive Glasses

This study aims to investigate the solubility of a series of titanium (TiO2)-containing bioactive glasses and their subsequent effect on cell viability. Five glasses were synthesized in the composition range SiO2-Na2O-CaO with 5 mol % of increments TiO2 substituted for SiO2. Glass solubility was investigated with respect to (1) exposed surface area, (2) particle size, (3) incubation time, and (4) compositional effects. Ion release profiles showed that sodium (Na+) presented high release rates after 1 day and were unchanged between 7 and 14 days. Calcium (Ca2+) release presented a significant change at each time period and was also composition dependent, where a reduction in Ca2+ release is observed with an increase in TiO2 concentration. Silica (Si4+) release did not present any clear trends while no titanium (Ti4+) was released. Cell numbers were found to increase up to 44%, compared to the growing control population, with a reduction in particle size and with the inclusion of TiO2 in the glass composition

One Health proof of concept: Bringing a transdisciplinary approach to surveillance for zoonotic viruses at the human-wild animal interface.

As the world continues to react and respond inefficiently to emerging infectious diseases, such as Middle Eastern Respiratory Syndrome and the Ebola and Zika viruses, a growing transdisciplinary community has called for a more proactive and holistic approach to prevention and preparedness - One Health. Such an approach presents important opportunities to reduce the impact of disease emergence events and also to mitigate future emergence through improved cross-sectoral coordination. In an attempt to provide proof of concept of the utility of the One Health approach, the US Agency for International Development's PREDICT project consortium designed and implemented a targeted, risk-based surveillance strategy based not on humans as sentinels of disease but on detecting viruses early, at their source, where intervention strategies can be implemented before there is opportunity for spillover and spread in people or food animals. Here, we share One Health approaches used by consortium members to illustrate the potential for successful One Health outcomes that can be achieved through collaborative, transdisciplinary partnerships. PREDICT's collaboration with partners around the world on strengthening local capacity to detect hundreds of viruses in wild animals, coupled with a series of cutting-edge virological and analytical activities, have significantly improved our baseline knowledge on the zoonotic pool of viruses and the risk of exposure to people. Further testament to the success of the project's One Health approach and the work of its team of dedicated One Health professionals are the resulting 90 peer-reviewed, scientific publications in under 5 years that improve our understanding of zoonoses and the factors influencing their emergence. The findings are assisting in global health improvements, including surveillance science, diagnostic technologies, understanding of viral evolution, and ecological driver identification. Through its One Health leadership and multi-disciplinary partnerships, PREDICT has forged new networks of professionals from the human, animal, and environmental health sectors to promote global health, improving our understanding of viral disease spillover from wildlife and implementing strategies for preventing and controlling emerging disease threats

Applying the CACAO Change Model to Promote Systemic Transformation in STEM

Since its inception in the Middle Ages, the university classroom can be characterized by students gathered around a sage who imparts his or her knowledge. However, the effective classroom of today looks vastly different: First-year engineering students not only learn basic engineering principles, but are also guided to consider their own inner values and motivations as they design and build adaptive devices for people with disabilities; students in a large chemistry lecture work animatedly together in small groups on inquiry-based activities while an instructor and teaching assistants circulate and guide their learning; students learning differential equations practice explicit metacognitive skills while problem-solving in class. Even though educational research, especially research that is targeted at STEM disciplines, demonstrates what most effectively engages students and supports their learning, many of today\u27s classrooms look much like they did a century ago, with a professor delivering a primarily one-way lecture and students passively sitting in seats bolted to the floor. At this juncture in history, colleges and universities face a public call to engage a more diverse representation of students in effective learning, persistence, and degree attainment, and to do so economically and efficiently. It is essential that institutions draw upon methods demonstrated to effectively increase student learning and success. Educational researchers have thoroughly explored the basic science in this area, and a body of literature documents effective evidence-based instructional practices, hereafter referred to as EBIPs