Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

This minireview explores mitochondria as a site for antibiotic-host interactions that lead to pathophysiologic responses manifested as nonantibacterial side effects. Mitochondrion-based side effects are possibly related to the notion that these organelles are archaic bacterial ancestors or commandeered remnants that have co-evolved in eukaryotic cells; thus, this minireview focuses on mitochondrial damage that may be analogous to the antibacterial effects of the drugs. Special attention is devoted to aminoglycosides, chloramphenicol, and fluoroquinolones and their respective single side effects related to mitochondrial disturbances. Linezolid/oxazolidinone multisystemic toxicity is also discussed. Aminoglycosides and oxazolidinones are inhibitors of bacterial ribosomes, and some of their side effects appear to be based on direct inhibition of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial ribosomes and gyrases/topoisomerases, respectively, both of which are present in mitochondria. However, the side effects of chloramphenicol and the fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria. Nonetheless, it appears that mitochondrion-associated side effects are a potential aspect of antibiotics whose targets are shared by prokaryotes and mitochondria—an important consideration for future drug design

Favorite Teacher or Worst Nightmare? Teachers who Crossed the Line

What kind of teacher sexually abuses her students? The current study, guided by critical theory, examines common characteristics of female high school teachers who sexually abuse their students. Extant research on teacher student relationships have found commonalities in the demographics of the offenders, their experience of adverse childhood experiences, common age of the victims, re-offense rates, and public perception of these types of crimes. The current study furthers previous research, by investigating their marital status at the time of the offense (married or not married), whether or not the offender has children, and school type (public or private). This study collected n=18 cases of female high school teachers in the state of Florida who are sexual offenders, and whose victims are their students. We have collected qualitative secondary data from news articles and investigative reports published by two websites: The Canadian Children’s Rights Council and The South Florida Sun Sentinel. Specific characteristics on each of the offenders were coded and inputted on Excel and data was analyzed using the phenomenological methodology. These characteristics include our three main constructs, in addition to offender as well as victim age. Results of the study will be discussed to help illuminate further common characteristics among these offenders, especially focusing on their relationship status, parental status, and school type in which they were employed at the time of the offense. Finally, implications on future research will be discussed

Methodology for reliable and reproducible cryopreservation of human cervical tissue

BACKGROUND: In order to conduct laboratory studies on donated cervical tissue at suitable times an effective and reliable cryopreservation protocol for cervical tissue is required. METHODS: An active freezing approach was devised utilising 10% dimethyl sulfoxide in foetal bovine serum as a cryoprotective agent with a cooling rate of 1 °C/min to -50 °C then 10 °C/min to -120 °C; a related thawing protocol was also optimised which would allow for the bio-banking of cervical tissue. Viability of freshly harvested cervical tissue was compared to frozen-thawed samples utilising colorimetric MTT assay. In parallel, fresh and freeze-thawed samples were cultured and tested on days 1, 7 and 14 to determine whether bio-banking had detrimental effects on tissue viability over time. RESULTS: Repeat testing revealed that tissue viability between fresh and freeze-thawed wasand freeze-thawed samples was comparable at all four time points (days 0, 1, 7 and 14) with no apparent reductions of viability, thus demonstrating this method of cryopreserving cervical tissue is reliable and reproducible, without detrimental effects on live tissue culture. We believe this methodology creates the opportunity for bio-banking donated cervical tissues, which aids improved experimental design and reduces time pressures and wastage

Can We Agree What Skilled Mindfulness-Based Teaching Looks Like? Lessons From Studying the MBI:TAC

BackgroundThe Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) is a widely used tool for assessing fidelity in mindfulness-based program (MBP) research and training. It also supports MBP teacher reflective and skill development. MBI:TAC assessors review MBP teaching and rate the teaching on 6 domains. The MBI:TAC yields individual domain and overall scores, using 6 levels of competence. Although the MBI:TAC is widely used in MBP research and training, research is at an early stage.ObjectiveWe developed and tested a method of training MBI:TAC assessors to use the tool reliably and examined interrater reliability of the tool.MethodsA total of 31 international senior MBP teachers were recruited to join an online training to build their skills in using the MBI:TAC. The training systematically and iteratively built familiarity and skills in assessing the 6 MBI:TAC domains. Qualitative and quantitative data on trainee's experience of the training were gathered. Interrater reliability in using the tool was tested each week of the training. At the end of the training, interrater reliability was tested by asking trainees to individually assess videos that they had not previously seen. Their ratings were compared to benchmark assessments, which had been established via consensus agreement between 4 expert users of the MBI:TAC.ResultsThe training was well received and appreciated, with some challenges experienced in applying the assessment methodology. Participants' ratings became progressively more in line with one another and the benchmark ratings during the training. At the end, interrater reliability was high (ranging from 0.67 to 1.0).ConclusionIt is possible for senior MBP trainers, coming from different regions in the world, to align toward common understandings of the elements of MBP teaching competence and program integrity. An assessor training methodology was tested, and the learning from this project has led to refinements for future delivery

Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction

BACKGROUND: Increased reactive oxygen species (ROS) production is involved in the process of adverse cardiac remodeling and development of heart failure after myocardial infarction (MI). NADPH oxidase-2 (Nox2) is a major ROS source within the heart and its activity increases after MI. Furthermore, genetic deletion of Nox2 is protective against post-MI cardiac remodeling. Nox2 levels may increase both in cardiomyocytes and endothelial cells and recent studies indicate cell-specific effects of Nox2, but it is not known which of these cell types is important in post-MI remodeling. METHODS AND RESULTS: We have generated transgenic mouse models in which Nox2 expression is targeted either to cardiomyocytes (cardio-Nox2TG) or endothelial cells (endo-Nox2TG). We here studied the response of cardio-Nox2TG mice, endo-Nox2TG mice and matched wild-type littermates (WT) to MI induced by permanent left coronary artery ligation up to 4weeks. Initial infarct size assessed by magnetic resonance imaging (MRI) and cardiac dysfunction were similar among groups. Cardiomyocyte hypertrophy and interstitial fibrosis were augmented in cardio-Nox2TG compared to WT after MI and post-MI survival tended to be worse whereas endo-Nox2TG mice showed no significant difference compared to WT. CONCLUSIONS: These results indicate that cardiomyocyte rather than endothelial cell Nox2 may have the more important role in post-MI remodeling

Gay and Bisexual Men's Willingness to Receive Anal Papanicolaou Testing

Objectives. We assessed the willingness of gay and bisexual men, who have high rates of anal cancer that might be prevented through regular screening, to receive anal Papanicolaou tests

Business models for circular sanitation: lessons from India

Providing safe sanitation in the developing world is still a major hurdle to achieving Sustainable Development Goal number six, with 61% of the global population lacking safely managed sanitation services. Circular economy in the context of sanitation focuses on the whole sanitation chain which includes the provision of toilets, the collection of waste, treatment and transformation into sanitation-derived products including fertiliser, fuel and clean water. As well as potentially reducing the cost of toilet provision, a circular economy approach also has the potential to enable positive environmental and health impacts, unlike other systems where waste may be discharged untreated into the environment. The implementation of a system level transformation is not simple, considering operator capacity, lack of funding, slowly growing acceptance by local communities, and a policy landscape which can be inconsistent in its support for the circular economy. As India invests in long-term infrastructure to improve citizens’ quality of life (e.g., Swachh Bharat Mission), it could incorporate circular economy principles into the design of infrastructure, creating effective urban nutrient and material cycles, enhancing economic development and welfare. This represents a significant opportunity for government and businesses in India to develop circular sanitation infrastructure to recover and valorise biological nutrients. After collecting information from five case studies across India, covering different treatment technologies, waste-derived products, markets and contexts; this research identifies the main barriers and enablers for circular sanitation business models to succeed. Whilst there were many different institutional and technological arrangements, common issues of managing and enforcing incoming waste and competing with chemical fertilisers were found

In situ characterization of CD4+ T cell behavior in mucosal and systemic lymphoid tissues during the induction of oral priming and tolerance

The behavior of antigen-specific CD4+ T lymphocytes during initial exposure to antigen probably influences their decision to become primed or tolerized, but this has not been examined directly in vivo. We have therefore tracked such cells in real time, in situ during the induction of oral priming versus oral tolerance. There were marked contrasts with respect to rate and type of movement and clustering between naive T cells and those exposed to antigen in immunogenic or tolerogenic forms. However, the major difference when comparing tolerized and primed T cells was that the latter formed larger and longer-lived clusters within mucosal and peripheral lymph nodes. This is the first comparison of the behavior of antigen-specific CD4+ T cells in situ in mucosal and systemic lymphoid tissues during the induction of priming versus tolerance in a physiologically relevant model in vivo