Organisms have gravity: taking an organism-centered approach in experimental biology.

When you take the time to observe another organism, there is a sort of gravity that can take hold, a mixture of curiosity and connection that expands and strengthens the more you interact with that organism. Yet, in research, a connection with one's study organism can, at times, feel countercultural. Study organisms are sometimes viewed more as tools to conveniently study biological questions. Here, we explicitly highlight the importance of organism-centered research not only in scientific discovery, but also in conservation and in the communication and perception of science.

Habitat and respiratory strategy effects on hypoxia performance in anuran tadpoles.

A critical component of animal conservation in a changing world is an understanding of the physiological resilience of animals to different conditions. In many aquatic animals, hypoxia (low environmental oxygen levels) is a regular occurrence, but the likelihood and severity of hypoxia varies across habitats. Fast-flowing, stream-like habitats are never hypoxic, so long as flow is maintained. Do animals from such habitats retain the capacity to survive hypoxic conditions? We use aquatic frog tadpoles to test the effects of natural habitat on performance in hypoxia in an experimental framework, finding that stream-living tadpoles have reduced performance in hypoxia. Tadpoles also vary in lung presence, with some species able to breathe air during hypoxia. We found that among lunged tadpoles, air-breathing rates increase in hypoxia in pond-living species but not stream-living species. Lung presence was also found to influence hypoxia performance, as lungless, stream-living tadpoles were found to be especially vulnerable to hypoxia, while pond-living, lungless tadpoles appeared largely resilient to hypoxia. We consider the ramifications of our findings on conservation outlooks and strategies for frogs and their tadpoles, suggesting that stream-living tadpoles, and especially lungless, stream-living tadpoles, may be particularly at risk to factors that reduce stream flow. Thus, a primary goal for conservation and management of species with stream-living tadpoles should be the maintenance of year-round streamflow, which oxygenates waters and prevents hypoxia.

The mechanics of air breathing in African clawed frog tadpoles, Xenopus laevis (Anura: Pipidae).

Frog larvae (tadpoles) undergo many physiological, morphological and behavioral transformations throughout development before metamorphosing into their adult form. The surface tension of water prevents small tadpoles from breaching the surface to breathe air (including those of Xenopus laevis), forcing them to acquire air using a form of breathing called bubble sucking. With growth, tadpoles typically make a behavioral/biomechanical transition from bubble sucking to breaching. Xenopus laevis tadpoles have also been shown to transition physiologically from conforming passively to ambient oxygen levels to actively regulating their blood oxygen. However, it is unknown whether these mechanical and physiological breathing transitions are temporally or functionally linked, or how both transitions relate to lung maturation and gas exchange competency. If these transitions are linked, it could mean that one biomechanical breathing mode (breaching) is more physiologically proficient at acquiring gaseous oxygen than the other. Here, we describe the mechanics and development of air breathing and the ontogeny of lung morphology in X. laevis throughout the larval stage and examine our findings considering previous physiological work. We found that the transitions from bubble sucking to breaching and from oxygen conforming to oxygen regulation co-occur in X. laevis tadpoles at the same larval stage (Nieuwkoop-Faber stages 53-56 and 54-57, respectively), but that the lungs do not increase significantly in vascularization until metamorphosis, suggesting that lung maturation, alone, is not sufficient to account for increased pulmonary capacity earlier in development. Although breach breathing may confer a respiratory advantage, we remain unaware of a mechanistic explanation to account for this possibility. At present, the transition from bubble sucking to breaching appears simply to be a consequence of growth. Finally, we consider our results in the context of comparative air-breathing mechanics across vertebrates.

Medical Stress and Fear of Death and Dying in a Medical Patient Population.

We explored the relationship between medical illness-related stress and fear of death and dying in a population of individuals with self-reported medical illnesses. Medically ill participants identified their level of stress related to their medical condition, their level of fear of death and dying, and what treatments they would most prefer for addressing any fear of death and dying as well as their medical illness-related stress. Participants' medical illness-related stress levels were high with an average endorsed score of 7.23 out of 10 (most extreme stress). The majority (70%) of participants endorsed "some," "a little," or "no fear" of death and dying. Overall, reported medical illness-related stress was not significantly correlated with fear of death and dying. Seventy-five percent of participants reported preferring psychotherapy or mindfulness interventions for addressing their stress. Psychotherapy, anti-anxiety medications, and meditation were the top three choices for addressing fear of death and dying.

Budget Impact Analysis of the Introduction of Injectable Prolonged-Release Buprenorphine on Opioid Use Disorder Care Resource Requirements.

OBJECTIVE: To assess budget impact of the introduction of prolonged-release buprenorphine (PRB) for care of opioid use disorder (OUD) over 1 year in a defined population. MATERIALS AND METHODS: A healthcare perspective, decision-tree model analysis of the cost of OUD care for a standard population was prepared to compare two scenarios: treatment of a population under the existing standard of care, or with the addition of PRB. The model assessed OUD-related direct costs (medication, delivery, psychosocial treatment), other services costs (harm reduction, general healthcare, social and justice services) and the impact of behaviors such as engaging with treatment and electing to use additional opioids "on top" of treatment regimens, and "dropping out" from treatment. RESULTS: Standard population definition (persons offered OUD care services) is based on a typical administrative region in England with general population of 400,000 citizens, 1,777 high-risk opioid users requiring treatment and 909 patients initiating treatment in a year. The cost to provide OUD care for 1 year under the current scenario (70% treated with methadone, 30% sublingual buprenorphine) is £19.7M. In scenarios with increased PRB adoption/reduced sublingual buprenorphine or oral methadone use, the cost reduction ranges from £0.2M to 0.7M. CONCLUSION: The assessment showed a reduction of overall costs after introduction of PRB.

Circumventing surface tension: tadpoles suck bubbles to breathe air.

The surface tension of water provides a thin, elastic membrane upon which many tiny animals are adapted to live and move. We show that it may be equally important to the minute animals living beneath it by examining air-breathing mechanics in five species (three families) of anuran (frog) tadpoles. Air-breathing is essential for survival and development in most tadpoles, yet we found that all tadpoles at small body sizes were unable to break through the water's surface to access air. Nevertheless, by 3 days post-hatch and only 3 mm body length, all began to breathe air and fill the lungs. High-speed macrovideography revealed that surface tension was circumvented by a novel behaviour we call 'bubble-sucking': mouth attachment to the water's undersurface, the surface drawn into the mouth by suction, a bubble 'pinched off' within the mouth, then compressed and forced into the lungs. Growing tadpoles transitioned to air-breathing via typical surface breaching. Salamander larvae and pulmonate snails were also discovered to 'bubble-suck', and two insects used other means of circumvention, suggesting that surface tension may have a broader impact on animal phenotypes than hitherto appreciated.

The mechanics of air breathing in gray tree frog tadpoles, Hyla versicolor (Anura: Hylidae).

We describe air-breathing mechanics in gray tree frog tadpoles (Hyla versicolor). We found that H. versicolor tadpoles breathe by 'bubble-sucking', a breathing mode typically employed by tadpoles too small to break the water's surface tension, in which a bubble is drawn into the buccal cavity and compressed into the lungs. In most tadpoles, bubble-sucking is replaced by breach breathing (breaking the surface to access air) at larger body sizes. In contrast, H. versicolor tadpoles bubble-suck throughout the larval period, despite reaching body sizes at which breaching is possible. Hyla versicolor tadpoles exhibit two bubble-sucking behaviors: 'single bubble-sucking', previously described in other tadpole species, is characterized by a single suction event followed by a compression phase to fill the lungs; 'double bubble-sucking' is a novel, apparently derived form of bubble-sucking that adds a second suction event. Hyla versicolor tadpoles transition from single bubble-sucking to double bubble-sucking at approximately 5.7 mm snout-vent length (SVL), which corresponds to a period of rapid lung maturation when they transition from low to high vascularization (6.0 mm SVL). Functional, behavioral and morphological evidence suggests that double bubble-sucking increases the efficiency of pulmonary gas exchange by separating expired, deoxygenated air from freshly inspired air to prevent mixing. Hyla versicolor, and possibly other hylid tadpoles, may have specialized for bubble-sucking in order to take advantage of this increased efficiency. Single and double bubble-sucking represent two- and four-stroke ventilation systems, which we discuss in the context of other anamniote air-breathing mechanisms.

The synthesis and biological evaluation of multifunctionalised derivatives of noscapine as cytotoxic agents.

Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well-known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, efforts have been made to design derivatives with improved potency. Herein, the synthesis of a series of noscapine analogues, which have been modified in the 6', 9', 1 and 7-positions, is described. In a previous study, replacement of the naturally occurring N-methyl group in the 6'-position with an N-ethylaminocarbonyl was shown to promote cell-cycle arrest and cytotoxicity against three cancer cell lines. Here, this modification has been combined with other structural changes that have previously been shown to improve anticancer activity, namely halo substitution in the 9'-position, regioselective O-demethylation to reveal a free phenol in the 7-position, and reduction of the lactone to the corresponding cyclic ether in the 1-position. The incorporation of new aryl substituents in the 9'-position was also investigated. The study identified interesting new compounds able to induce G2/M cell-cycle arrest and that possess cytotoxic activity against the human prostate carcinoma cell line PC3, the human breast adenocarcinoma cell line MCF-7, and the human pancreatic epithelioid carcinoma cell line PANC-1. In particular, the ethyl urea cyclic ether noscapinoids and a compound containing a 6'-ethylaminocarbonyl along with 9'-chloro, 7-hydroxy and lactone moieties exhibited the most promising biological activities, with EC50 values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.

Supporting cancer patients in Jamaica--a needs assessment survey.

OBJECTIVE: Global cancer incidence is rising rapidly particularly in the developing world where a majority of people present with advanced disease. In the English-speaking Caribbean, there is very little published data on the needs of cancer patients, their caregivers or those of allied health professionals. The research team sought to redress this balance by undertaking a needs assessment survey in the South Eastern Health Region of Jamaica to identify unmet needs and to make recommendations for improved service delivery. METHODS: A mixed methods, cross-sectional study design was used involving formal and semi-formal interviews and focus group discussions. RESULTS: The study results indicated that there were significant barriers to accessing healthcare. These included prohibitive costs of diagnosis and treatment, a mistrust of and poor communication with doctors, compounded by people's fears, belief in folk wisdom and lack of knowledge about cancer. Recommendations offered by the study participants focussed on a community-based model of support to address the multiple needs of people facing life-limiting illness and their caregivers. Healthcare practitioners recommended the development of specific policies, targeting, in particular improved drug availability and palliative care education in order to guide development of appropriate services for the large numbers of cancer patients in need. CONCLUSION: A multiplicity of unmet needs was identified by cancer patients, their caregivers and allied health professionals. Recommendations by study participants and the authors echoed the guidelines as set out by the World Health Organization (WHO) in its 1990 Public Health Model for the integration of palliative care into existing healthcare systems.

Supporting cancer patients in Jamaica: a needs assessment survey / Apoyo a los pacientes de cáncer en Jamaica: una encuesta para la evaluación de las necesidades

OBJECTIVE: Global cancer incidence is rising rapidly, particularly in the developing world where a majority of people present with advanced disease. In the English-speaking Caribbean, there is very little published data on the needs of cancer patients, their caregivers or those of allied health professionals. The research team sought to redress this balance by undertaking a needs assessment survey in the South Eastern Health Region of Jamaica to identify unmet needs and to make recommendations for improved service delivery. METHODS: A mixed methods, cross-sectional study design was used involving formal and semi-formal interviews and focus group discussions. RESULTS: The study results indicated that there were significant barriers to accessing healthcare. These included prohibitive costs of diagnosis and treatment, a mistrust of, and poor communication with doctors, compounded by people's fears, belief in folk wisdom and lack of knowledge about cancer. Recommendations offered by the study participants focussed on a community-based model of support to address the multiple needs of people facing life-limiting illness and their caregivers. Healthcare practitioners recommended the development of specific policies, targeting, in particular, improved drug availability and palliative care education in order to guide development of appropriate services for the large numbers of cancer patients in need. CONCLUSION: A multiplicity of unmet needs was identified by cancer patients, their caregivers and allied health professionals. Recommendations by study participants and the authors echoed the guidelines as set out by the World Health Organization (WHO) in its 1990 Public Health Model for the integration of palliative care into existing healthcare systems.

OBJETIVO: La incidencia de cáncer global está aumentado rápidamente, particularmente en el mundo en vías de desarrollo, dónde un gran número de personas se presentan con la enfermedad en estado avanzado. En el Caribe angloparlante, se ha publicado muy poca información sobre las necesidades de los pacientes de cáncer, sus cuidadores o los profesionales de salud asociados. El equipo de investigación buscó restablecer el equilibrio emprendiendo un estudio de evaluación de las necesidades en la Región de Salud Suroriental de Jamaica, para identificar las necesidades no satisfechas y hacer recomendaciones encaminadas a mejorar la prestación de servicios. MÉTODOS: Se empleo un diseño de estudio transversal con métodos mixtos, contentivo de entrevistas formales y semi-formales así como discusiones de grupos focales. RESULTADOS: Los resultados del estudio indicaron que había barreras considerables para el acceso a la atención a la salud. Estas comprendían costos prohibitivos para el diagnóstico y el tratamiento, desconfianza y pobre comunicación con los doctores, agravada por los miedos de la gente, la creencia en la sabiduría popular, y la falta de conocimientos sobre el cáncer. Las recomendaciones ofrecidas por los participantes en el estudio se centran en un modelo basado en la comunidad. Este modelo permite abordar las múltiples necesidades de las personas que enfrentan enfermedades limitantes de la vida, así como las necesidades de sus cuidadores. Los practicantes de cuidados de la salud recomendaron el desarrollo de políticas específicas, encaminadas especialmente a mejorar la disponibilidad de medicamentos y educación de cuidados paliativos para guiar el desarrollo de servicios apropiados para el gran número de pacientes necesitados, enfermos de cáncer. CONCLUSIÓN: Se identificaron una multiplicidad de necesidades no satisfechas, por parte de los pacientes de cáncer, sus cuidadores y profesionales de salud asociados. Las recomendaciones hechas por los participantes en el estudio y los autores, siguieron al pie de la letra los lineamientos trazados por la Organización Mundial de la Salud (OMS) en su Modelo de Salud Pública de 1990 para la integración del cuidado paliativo en los sistemas de cuidado de salud existentes.