Clinical pharmacology and therapeutics

Pharmacotherapeutics is an important element of space medicine practice. Assessing health risks, developing countermeasures, selecting relevant supplies for medical kits and providing appropriate training for crew members on the use of medical kits prior to the mission start are all major contributors of mission success. In this chapter, the standards applicable to clinical pharmacy practice are discussed, and best practices recommended. A review of existing evidence on the incidence and management of clinical conditions that have occurred during space flight is presented along with results of research conducted of drugs under the influence of microgravity. Ground-based models, such as bed-rest and animal surrogate studies, supplement and validate clinical observations from space missions. Space flight is associated with morphological and profound physiological changes, including alterations in fluid, electrolytes, and gastrointestinal function capable of affecting the pharmacokinetics—primarily after oral administration of medications. Exposure to the space environment, particularly radiation, can also shorten the shelf life of many chemical preparations, potentially affecting their efficacy, altering their bioavailability. Special packaging, radiation insulation of the medical storage area, and periodic return of samples to determine pharmacologic activity of medications is possible in Low Earth Orbit, such as the International Space Station, which offers a unique test-bed environment. Information on the absorption, distribution, metabolism, and excretion of major drug categories in the space microgravity environment is incomplete. Since research evidence on pharmacotherapeutics in space is sparse, clinical practitioners rely primarily on observational and anecdotal evidence compiled from individual crew opinions gathered from prior missions

Population structure, propagule pressure, and conservation biogeography in the sub-Antarctic: lessons from indigenous and invasive springtails

The patterns in and the processes underlying the distribution of invertebrates among Southern Ocean islands and across vegetation types on these islands are reasonably well understood. However, few studies have examined the extent to which populations are genetically structured. Given that many sub-Antarctic islands experienced major glaciation and volcanic activity, it might be predicted that substantial population substructure and little genetic isolation-by-distance should characterize indigenous species. By contrast, substantially less population structure might be expected for introduced species. Here, we examine these predictions and their consequences for the conservation of diversity in the region. We do so by examining haplotype diversity based on mitochondrial cytochrome c oxidase subunit I sequence data, from two indigenous (Cryptopygus antarcticus travei, Tullbergia bisetosa) and two introduced (Isotomurus cf. palustris, Ceratophysella denticulata) springtail species from Marion Island. We find considerable genetic substructure in the indigenous species that is compatible with the geological and glacialogical history of the island. Moreover, by employing ecological techniques, we show that haplotype diversity is likely much higher than our sequenced samples suggest. No structure is found in the introduced species, with each being represented by a single haplotype only. This indicates that propagule pressure is not significant for these small animals unlike the situation for other, larger invasive species: a few individuals introduced once are likely to have initiated the invasion. These outcomes demonstrate that sampling must be more comprehensive if the population history of indigenous arthropods on these islands is to be comprehended, and that the risks of within- and among-island introductions are substantial. The latter means that, if biogeographical signal is to be retained in the region, great care must be taken to avoid inadvertent movement of indigenous species among and within islands. Thus, quarantine procedures should also focus on among-island movements.Ctr Invas Bio

Agglomeration of celecoxib by quasi emulsion solvent diffusion method: effect of stabilizer

Purpose: The quasi-emulsion solvent diffusion (QESD) has evolved into an effective technique to manufacture agglomerates of API crystals. Although, the proposed technique showed benefits, such as cost effectiveness, that is considerably sensitive to the choice of a stabilizer, which agonizes from a absence of systemic understanding in this field. In the present study, the combination of different solvents and stabilizers were compared to investigate any connections between the solvents and stabilizers. Methods: Agglomerates of celecoxib were prepared by QESD method using four different stabilizers (Tween 80, HPMC, PVP and SLS) and three different solvents (methyl acetate, ethyl acetate and isopropyl acetate). The solid state of obtained particles was investigated by differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy. The agglomerated were also evaluated in term of production yield, distribution of particles and dissolution behavior. Results: The results showed that the effectiveness of stabilizer in terms of particle size and particle size distribution is specific to each solvent candidate. A stabilizer with a lower HLB value is preferred which actually increased its effectiveness with the solvent candidates with higher lipophilicity. HPMC appeared to be the most versatile stabilizer because it showed a better stabilizing effect compared to other stabilizers in all solvents used. Conclusion: This study demonstrated that the efficiency of stabilizers in forming the celecoxib agglomerates by QESD was influenced by the HLB of the stabilizer and lipophilicity of the solvents

Autism and the broad autism phenotype: familial patterns and intergenerational transmission

Abstract Background Features of the Broad Autism Phenotype (BAP) are disproportionately prevalent in parents of a child with autism, highlighting familial patterns indicative of heritability. It is unclear, however, whether the presence of BAP features in both parents confers an increased liability for autism. The current study explores whether the presence of BAP features in two biological parents occurs more frequently in parents of a child with autism relative to comparison parents, whether parental pairs of a child with autism more commonly consist of one or two parents with BAP features, and whether these features are associated with severity of autism behaviors in probands. Method Seven hundred eleven parents of a child with an autism spectrum disorder and 981 comparison parents completed the Broad Autism Phenotype Questionnaire. Parents of a child with autism also completed the Social Communication Questionnaire. Results Although parental pairs of a child with autism were more likely than comparison parental pairs to have both parents characterized by the presence of the BAP, they more commonly consisted of a single parent with BAP features. The presence of the BAP in parents was associated with the severity of autism behaviors in probands, with the lowest severity occurring for children of parental pairs in which neither parent exhibited a BAP feature. Severity did not differ between children of two affected parents and those of just one. Conclusions Collectively, these findings indicate that parental pairs of children with autism frequently consist of a single parent with BAP characteristics and suggest that future studies searching for implicated genes may benefit from a more narrow focus that identifies the transmitting parent. The evidence of intergenerational transmission reported here also provides further confirmation of the high heritability of autism that is unaccounted for by the contribution of de novo mutations currently emphasized in the field of autism genetics

Historical geography II: traces remain

The second report in this series turns to focus on the trace in relation to life-writing and biography in historical geography and beyond. Through attention to tracing journeys, located moments and listening to the presence of ghosts (Ogborn, 2005), this report seeks to highlight the range of different ways in which historical geographers have explored lives, deaths, and their transient traces through varied biographical terrains. Continuing to draw attention in historical geography to the darkest of histories, this piece will pivot on moments of discovering the dead to showcase the nuanced ways in which historical geography is opening doors into uncharted lives and unspoken histories

Baby-Led Weaning: The Evidence to Date

Purpose of ReviewInfants are traditionally introduced to solid foods using spoon-feeding of specially prepared infant foods.Recent FindingsHowever, over the last 10–15 years, an alternative approach termed ‘baby-led weaning’ has grown in popularity. This approach involves allowing infants to self-feed family foods, encouraging the infant to set the pace and intake of the meal. Proponents of the approach believe it promotes healthy eating behaviour and weight gain trajectories, and evidence is starting to build surrounding the method. This review brings together all empirical evidence to date examining behaviours associated with the approach, its outcomes and confounding factors.SummaryOverall, although there is limited evidence suggesting that a baby-led approach may encourage positive outcomes, limitations of the data leave these conclusions weak. Further research is needed, particularly to explore pathways to impact and understand the approach in different contexts and populations

Managing healthcare budgets in times of austerity: the role of program budgeting and marginal analysis

Given limited resources, priority setting or choice making will remain a reality at all levels of publicly funded healthcare across countries for many years to come. The pressures may well be even more acute as the impact of the economic crisis of 2008 continues to play out but, even as economies begin to turn around, resources within healthcare will be limited, thus some form of rationing will be required. Over the last few decades, research on healthcare priority setting has focused on methods of implementation as well as on the development of approaches related to fairness and legitimacy and on more technical aspects of decision making including the use of multi-criteria decision analysis. Recently, research has led to better understanding of evaluating priority setting activity including defining ‘success’ and articulating key elements for high performance. This body of research, however, often goes untapped by those charged with making challenging decisions and as such, in line with prevailing public sector incentives, decisions are often reliant on historical allocation patterns and/or political negotiation. These archaic and ineffective approaches not only lead to poor decisions in terms of value for money but further do not reflect basic ethical conditions that can lead to fairness in the decision-making process. The purpose of this paper is to outline a comprehensive approach to priority setting and resource allocation that has been used in different contexts across countries. This will provide decision makers with a single point of access for a basic understanding of relevant tools when faced with having to make difficult decisions about what healthcare services to fund and what not to fund. The paper also addresses several key issues related to priority setting including how health technology assessments can be used, how performance can be improved at a practical level, and what ongoing resource management practice should look like. In terms of future research, one of the most important areas of priority setting that needs further attention is how best to engage public members

Childhood/adolescent smoking and adult smoking and cessation: The International Childhood Cardiovascular Cohort (i3C) Consortium

Background: Despite declining US adolescent smoking prevalence from 40% among 12th graders in 1995 to around 10% in 2018, adolescent smoking is still a significant problem. Using the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes 7 international cohorts recruited in childhood and followed into adulthood, the present study was designed to confirm the important relation between adolescent smoking and daily adult smoking and present new data on adult smoking into the forties and comparison of smoking in the United States, Finland, and Australia. Methods and Results: Childhood smoking experience during ages 6 to 19 in the 1970s and 1980s was classifiable in 6687 i3C participants who also provided smoking status in their twenties and forties through 2011-2018. Prevalence of daily smoking in their twenties was directly related to degree of smoking during adolescence and inversely related to the age at which that smoking experience occurred (P trend, P trend, Conclusions: These long-term follow-up data show that smoking intensity increased throughout adolescence. Prevalence of adult smoking and cessation by the forties were both correlated with levels of childhood smoking intensity. These data lend support to preventive strategies designed to reduce, delay, or eliminate any youth access to cigarettes

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses