Philosophy as a way of life, spiritual exercises, and palliative care

This paper proposes that resources from philosophy as a way of life (PWL), in particular the prescription of targeted ‘spiritual exercises’ (Hadot) can be used in palliative counselling, addressing Alexandrova's critique that philosophy as ‘big picture’ theories alone are insufficient. Part I shows how the disciplines of philosophy and medicine for a long time intersected, in particular in competing prescriptive notions of ‘regimen’ or ‘way of life’ (diaitês) in the ancient world, in which philosophy was considered widely as PWL. Part II applies PWL work on the ancient philosophical spiritual exercises to contemporary clinical settings. We show how six ancient spiritual exercises respond to patients' needs as persons, whose quality of life is importantly shaped by their beliefs and sense-making, as they face profound existential or spiritual challenges, as well as forms of physical disability and diminished capabilities which they may never have previously countenanced

Improving outcome in out-of-hospital cardiac arrest: impact of bystander cardiopulmonary resuscitation and prehospital physician care

Evidence for the impact of prehospital, physician-delivered advanced cardiac life support (ACLS) on survival from out-of-hospital cardiac arrest is conflicting. The prospective observational study by Yasunaga and co-workers demonstrates an improved survival at 1 month associated with prehospital physician-delivered ACLS over emergency life-saving technician-delivered ACLS. These effects are additive to the survival benefit seen with bystander-initiated cardiopulmonary resuscitation (BCPR) compared with no BCPR. The present commentary places these findings in the context of the existing literature and discusses some of the unresolved controversies

Psychosocial Determinants of Health Behaviour Change in an E-Counseling Intervention for Hypertension

We evaluated the influence of psychological stress and depression on motivation to adhere to recommended guidelines for exercise and diet. This study was conducted within a larger e-counseling trial. Subjects diagnosed with hypertension (n = 387, age = 44–74 years, 59% female) completed assessments at baseline and within 2 weeks after a 4-month intervention period. Outcomes included mean level of readiness to change diet and exercise and symptoms of depression and stress. Per protocol analysis defined e-counseling support as follows: ≥8 e-mails = therapeutic dose, 1–7 e-mails = subtherapeutic dose, and 0 e-mails = Controls. Baseline adjusted symptoms of depression and stress were inversely correlated with improvement in exercise (partial R = −.14, P = .01, and partial R = −.17, P = .01, resp.) but not diet or e-counseling. Subjects who received a therapeutic dose of e-counseling demonstrated greater readiness for diet adherence versus Controls (P = .02). Similarly, subjects receiving a therapeutic level of e-counseling demonstrated significantly greater readiness for exercise adherence versus Controls (P = .04). In sum, e-counseling is associated with improved motivation to adhere to exercise and diet among patients with hypertension, independent of symptoms of psychological stress and depression

Proliferation tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells.

Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation

DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity.

An individual malignant tumor is composed of a heterogeneous collection of single cells with distinct molecular and phenotypic features, a phenomenon termed intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for cancer treatment, motivating the need for combination therapies. Single-cell technologies are now available to guide effective drug combinations by accounting for intratumoral heterogeneity through the analysis of the signaling perturbations of an individual tumor sample screened by a drug panel. In particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single-cell technology that enables the simultaneous measurements of multiple ([Formula: see text]40) intracellular and surface markers at the level of single cells for hundreds of thousands of cells in a sample. We developed a computational framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF single-drug perturbation data for the purpose of individualizing drug combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number of drugs that produce the maximal desired intracellular effects based on nested effects modeling. We demonstrate the performance of DRUG-NEM using single-cell drug perturbation data from tumor cell lines and primary leukemia samples

Effects of Low-Level Artificial Light at Night on Kentucky Bluegrass and Introduced Herbivore

Increasing evidence suggests that artificial light at night (ALAN) can negatively impact organisms. However, most studies examine the impacts of ALAN on a single species or under high levels of artificial light that are infrequent or unrealistic in urban environments. We currently have little information on how low levels of artificial light emanating from urban skyglow affect plants and their interactions with herbivores. We examined how low levels of ALAN affect grass and insects, including growth rate, photosynthesis, and stomatal conductance in grass, and foraging behavior and survival in crickets. We compared growth and leaf-level gas exchange of Kentucky Bluegrass (Poa pratensis) under low-levels of ALAN (0.3 lux) and starlight conditions (night light at 0.001 lux). Furthermore, each light treatment was divided into treatments with and without house crickets (Acheta domesticus). Without crickets present, bluegrass grown under artificial light at night for three weeks grew taller than plants grown under natural night light levels. Once crickets were introduced at the end of week three, grass height decreased resulting in no measurable effects of light treatment. There were no measurable differences in grass physiology among treatments. Our results indicate that low levels of light resulting from skyglow affect plant growth initially. However, with herbivory, ALAN effects on grass may be inconsequential. Gaining an understanding of how ALAN affects plant-insect interactions is critical to predicting ecological and evolutionary consequences of anthropogenic disturbance

A method for exposing rodents to resuspended particles using whole-body plethysmography

BACKGROUND: Epidemiological studies have reported increased risks of cardiopulmonary-related hospitalization and death in association with exposure to elevated levels of particulate matter (PM) across a wide range of urban areas. In response to these findings, researchers have conducted animal inhalation exposures aimed at reproducing the observed toxicologic effects. However, it is technically difficult to quantitate the actual amount of PM delivered to the lung in such studies, and dose is frequently estimated using default respiration parameters. Consequently, the interpretation of PM-induced effects in rodents exposed via whole-body inhalation is often compromised by the inability to determine deposited dose. To address this problem, we have developed an exposure system that merges the generation of dry, aerosolized particles with whole-body plethysmography (WBP), thus permitting inhalation exposures in the unrestrained rat while simultaneously obtaining data on pulmonary function. RESULTS: This system was validated using an oil combustion-derived particle (HP12) at three nominal concentrations (3, 12, and 13 mg/m(3)) for four consecutive exposure days (6 hr/day); a single 6-hour exposure to 13 mg/m(3 )of HP12 was also conducted. These results demonstrated that the system was both reliable and consistent over these exposure protocols, achieving average concentrations that were within 10% of the targeted concentration. In-line filters located on the exhaust outlets of individual WBP chambers showed relative agreement in HP12 mass for each day and were not statistically different when compared to one another (p = 0.16). Temperatures and relative humidities were also similar between chambers during PM and air exposures. Finally, detailed composition analyses of both HP12 filter and bulk samples showed that grinding and aerosolization did not change particle chemistry. CONCLUSION: The results of this study demonstrate that it is possible to expose rodents to resuspended, dry PM via whole-body inhalation while these animals are maintained in WBP chambers. This new methodology should significantly improve the ability to assess dosimetry under minimally stressful exposure conditions

Recyclable NHC catalyst for the development of a generalized approach to continuous Buchwald-Hartwig reaction and work-up

A generalized approach to the optimization and implementation of Buchwald-Hartwig reactions in flow is reported, through the combination of three key factors: a highly active palladium catalyst; a universal approach for continuous work-up and purification, and a methodology for catalyst recycling and reuse. The palladium N-heterocyclic carbene (NHC) pre-catalyst [Pd(IPr*)(cin)Cl] 4 (IPr* = 1,3-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene; cin = η3-cinnamyl) is an excellent choice for continuous Buchwald-Hartwig reactions, due to its inherent high activity and stability. In preparation for running this reaction in flow (published concurrently), a detailed study has been carried out into its water stability, ultimately allowing the recycling of the catalyst in the organic phase up to 3 times in batch mode. A “right-first-time” work-up methodology has also been developed, resulting in a universal protocol that allows the selective extraction of the Buchwald-Hartwig product into the aqueous stream as a salt, while retaining the aryl bromide starting material in the organic stream with the catalyst, thus negating the requirement for further purification. It is therefore envisaged that this approach will particularly amenable to exploitation in the Pharmaceutical industry. An optimized, scalable synthesis of [Pd(IPr*)(cin)Cl] is also reported on multi-hundred gram scale