1,000 research outputs found

    Cornea organoids from human induced pluripotent stem cells.

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    The cornea is the transparent outermost surface of the eye, consisting of a stratified epithelium, a collagenous stroma and an innermost single-cell layered endothelium and providing 2/3 of the refractive power of the eye. Multiple diseases of the cornea arise from genetic defects where the ultimate phenotype can be influenced by cross talk between the cell types and the extracellular matrix. Cell culture modeling of diseases can benefit from cornea organoids that include multiple corneal cell types and extracellular matrices. Here we present human iPS cell-derived organoids through sequential rounds of differentiation programs. These organoids share features of the developing cornea, harboring three distinct cell types with expression of key epithelial, stromal and endothelial cell markers. Cornea organoid cultures provide a powerful 3D model system for investigating corneal developmental processes and their disruptions in diseased conditions

    Quantum Chemical Lipophilicities of Antimalarial Drugs in Relation to Terminal Half-Life

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    According to the WHO, artemisinin-based combination therapies (ACTs) have been integral to the recent reduction in deaths due to Plasmodium falciparum malaria. ACT-resistant strains are an emerging problem and have evolved altered developmental stages, reducing exposure of the most susceptible stages to artemisinin drugs in popular ACTs. Lipophilicity, log Kow, is a guide in understanding and predicting pharmacokinetic properties such as terminal half-life which alters drug exposure. Consistent log Kow values are not necessarily available for artemisinin derivatives designed to extend terminal half-life, increase bioavailability, and reduce neurotoxicity. For other drugs used in ACTs, an assortment of experimental and computational log Kow values are available in the literature and in some cases, do not account for subtle but important differences between closely related structures such as between diastereomers. Quantum chemical methods such as density functional theory (DFT) used with an implicit solvent model allow for consistent comparison of physical properties including log Kow and distinguish between closely related structures. To this end, DFT, B3LYP/6-31G(d), with an implicit solvent model (SMD) was used to compute ΔGowo and ΔGvowo for 1-octanol–water and olive oil–water partitions, respectively, for 21 antimalarial drugs: 12 artemisinin-based, 4 4-aminoquinolines and structurally similar pyronaridine, and 4 amino alcohols. The computed ΔGowo was close to ΔGowo calculated from experimental log Kow values from the literature where available, with a mean signed error of 2.3 kJ/mol and mean unsigned error of 3.7 kJ/mol. The results allow assignment of log Kow for α-and β-diastereomers of arteether, and prediction of log Kow for β-DHA and five experimental drugs. Linear least square analysis of log Kow and log Kvow versus terminal elimination half-life showed strong linear relationships, once the data points for the 4-aminoquinoline drugs, mefloquine and pyronaridine were found to follow their own linear relationship, which is consistent with their different plasma protein binding. The linear relationship between the computed log Kvow and terminal elimination half-life was particularly strong, R2 = 0.99 and F = 467, and can be interpreted in terms of a simple pharmacokinetic model. Terminal elimination half-life for β-DHA and four experimental artemisinin drugs were estimated based on this linear relationship between log Kvow and terminal t1/2. The computed log Kow and log Kvow values for epimers α- and β-DHA and α and β-arteether provide physical data that may be helpful in understanding their different pharmacokinetics and activity based on their different molecular geometries. Relative solubility of quinine and quinidine are found to be sensitive to thermal corrections to enthalpy and to vibrational entropy and do not follow the general trend of longer terminal t1/2 with greater predicted log Kow. Geometric relaxation of α- and β-DHA in solvent and inclusion of thermal correction for enthalpy and entropy results in correct prediction that α-DHA is favored in aqueous environments compared to β-DHA. Predictions made regarding experimental drugs have implications regarding their potential use in response to artemisinin drug-resistant strains

    Reinterpreting the Pollen Data from Dos Cabezas

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    The published pollen analysis of the Dos Cabezas giants, Geyer et al. (2003), lists variety of purported dietary pollen types. The paper also hypothesises that the giants were poisoned with plant toxins. We have severe reservations about the pollen evidence of diet and poisoning. We suggest that the analysts made several errors in their interpretation. Firstly, some of the discovered pollen types are not prehistoric endemics to the Dos Cabezas region of coastal Peru. These include the pollen of fava beans (cultivated in the Old World), and specified species of agave and sage. We believe that some or all of the identifications of pollen from arracacha, maca, yuca, oca, potato, peanut, ciruela and tarwi are in error based on the distance they grow from Dos Cabezas and/or their ecological/pollination requirements. We think that it is unlikely that the giants were poisoned because the poisons made from six poisonous plants are not made from the flowers and five of them grow on the opposite side of the Andes from Dos Cabezas. We present an alternative dietary interpretation of the Dos Cabezas giants and suggest methods by which palynological analysis could be improved

    Pharmacy-Based Travel Health Services in the United States

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    The aim of this paper is to review pharmacy laws and regulations, pharmacist training, clinic considerations, and patient care outcomes regarding pharmacy-based travel health services in the United States. Pharmacists and pharmacies in the United States are highly visible and accessible to the public, and have long been regarded as a source for immunization services. As international travel continues to increase and grow in popularity in this country, there is a pressing need for expanded access to preventative health services, including routine and travel vaccinations, as well as medications for prophylaxis or self-treatment of conditions that may be acquired overseas. In the United States, the scope of pharmacy practice continues to expand and incorporate these preventable health services to varying degrees on a state-by-state level. A literature review was undertaken to identify published articles on pharmacist- or pharmacy-based travel health services or care in the United States. The results of this paper show that pharmacists can help to increase access to and awareness of the need for these services to ensure that patients remain healthy while traveling abroad, and that they do not acquire a travel-related disease while on their trip. For those pharmacists interested in starting a travel health service, considerations should be made to ensure that they have the necessary training, education, and skill set in order to provide this specialty level of care, and that their practice setting is optimally designed to facilitate the service. While there is little published work available on pharmacy or pharmacist-provided travel health services in the United States, outcomes from published studies are positive, which further supports the role of the pharmacist in this setting

    Impact of Empire Expansion on Household Diet: The Inka in Northern Chile's Atacama Desert

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    The impact of expanding civilization on the health of American indigenous societies has long been studied. Most studies have focused on infections and malnutrition that occurred when less complex societies were incorporated into more complex civilizations. The details of dietary change, however, have rarely been explored. Using the analysis of starch residues recovered from coprolites, here we evaluate the dietary adaptations of indigenous farmers in northern Chile's Atacama Desert during the time that the Inka Empire incorporated these communities into their economic system. This system has been described as “complementarity” because it involves interaction and trade in goods produced at different Andean elevations. We find that as local farming societies adapted to this new asymmetric system, a portion of their labor had to be given up to the Inka elite through a corvée tax system for maize production. In return, the Inka system of complementarity introduced previously rare foods from the Andean highlands into local economies. These changes caused a disruption of traditional communities as they instituted a state-level economic system on local farmers. Combined with previously published infection information for the same populations under Inka rule, the data suggest that there may have been a dual health impact from disruption of nutrition and introduction of crowd disease

    Impact of empire expansion on household diet: the Inka in Northern Chile\u27s Atacama Desert

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    The impact of expanding civilization on the health of American indigenous societies has long been studied. Most studies have focused on infections and malnutrition that occurred when less complex societies were incorporated into more complex civilizations. The details of dietary change, however, have rarely been explored. Using the analysis of starch residues recovered from coprolites, here we evaluate the dietary adaptations of indigenous farmers in northern Chile\u27s Atacama Desert during the time that the Inka Empire incorporated these communities into their economic system. This system has been described as complementarity because it involves interaction and trade in goods produced at different Andean elevations. We find that as local farming societies adapted to this new asymmetric system, a portion of their labor had to be given up to the Inka elite through a corvée tax system for maize production. In return, the Inka system of complementarity introduced previously rare foods from the Andean highlands into local economies. These changes caused a disruption of traditional communities as they instituted a state-level economic system on local farmers. Combined with previously published infection information for the same populations under Inka rule, the data suggest that there may have been a dual health impact from disruption of nutrition and introduction of crowd disease

    The U.S. Travel Health Pharmacists’ Role in a Post-COVID-19 Pandemic Era

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    Background: Many countries have enforced strict regulations on travel since the emergence of the SARS-CoV-2 (COVID-19) pandemic in December 2019. However, with the development of several vaccines and tests to help identify it, international travel has mostly resumed in the United States (US). Community pharmacists have long been highly accessible to the public and are capable of providing travel health services and are in an optimal position to provide COVID-19 patient care services to those who are now starting to travel again. Objectives: (1) To discuss how the COVID-19 pandemic has changed the practice of travel health and pharmacist provided travel health services in the US and (2) to discuss the incorporation COVID-19 prevention measures, as well as telehealth and other technologies, into travel health care services. Methods: A literature review was undertaken utilizing the following search engines and internet websites: PubMed, Google Scholar, Centers for Disease Control Prevention (CDC),World Health Organization (WHO), and the United States Department of Health and Human Services to identify published articles on pharmacist and pharmacy-based travel health services and patient care in the US during the COVID-19 pandemic. Results: The COVID-19 pandemic has changed many country’s entry requirements which may now include COVID-19 vaccination, testing, and/or masking requirements in country. Telehealth and other technological advancements may further aid the practice of travel health by increasing patient access to care. Conclusions: Community pharmacists should consider incorporating COVID-19 vaccination and testing services in their travel health practices in order to meet country-specific COVID-19 entry requirements. Further, pharmacists should consider utilizing telehealth and other technologies to increase access to care while further limiting the potential spread and impact of COVID-19

    Starch grains and Phytoliths in human dental calculus: contribution to the study of life style and subsistence at Sambaqui groups in Brazilian southern coast

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    Este artigo tem por objetivo apresentar os resultados da recuperação e análise de micro-vestígios vegetais retidos em cálculos dentários de grupos de pescadores-coletores do litoral sul do Brasil. Apresenta também os resultados das relações mantidas entre grânulos de amido e cárie, e entre fitólitos e desgaste dentário. Através da dissolução química de cálculos dentários foram recuperados microvestígios vegetais em todos os indivíduos estudados. Foi evidenciado o consumo de alimentos amiláceos em todas as séries esqueléticas estudadas, demonstrando independência entre dieta com aporte de produtos vegetais e utilização de cerâmica. Foram encontrados resultados sugestivos de padrões de escolha de alimentos diferenciados entre os grupos e evidências de contato entre litoral e planalto.The aim of this paper is to present the analysis of micro-residues recovered from fishers-gatherers dental calculus. All analyzed groups are from southern Brazilian shell-mounds. The relationships found between microresidues and dental physiopathology is presented too. The dietary consumption of starchy vegetables was evidenced in all studied groups, independently of the presence of ceramic in the sites. The results point to different choice patterns concerning edible vegetables. The contact between seashore and inland are evidenced too

    From Web 1.0 to Web 2.0 and back - How did your Grandma use to tag?

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    We consider the applicability of terms extracted from anchortext as a source of Web page descriptions in the form of tags. With a relatively simple and easy-to-use method, we show that anchortext significantly overlaps with tags obtained from the popular tagging portal del.icio.us. Considering the size and diversity of the user community potentially involved in social tagging, this observation is rather surprising. Furthermore, we show by an evaluation using human-created relevance assessments the general suitability of the anchortext tag generation in terms of user-perceived precision values. The awareness of this easy-to-obtain source of tags could trigger the rise of new tagging portals pushed by this automatic bootstrapping process or be applied in already existing portals to increase the number of tags per page by merely looking at the anchortext which exists anyway

    Developing a scale to explore self-regulatory approaches to assessment and feedback with academics in higher education

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    Introduction: Students need to acquire high level self-regulatory skills if they are to be successful within higher education, and academics need support in facilitating this. In this article we explore how the current research gap between knowledge of self-regulatory assessment and feedback (SRAF) practices, and academics’ professional training in it can be bridged. Methods: SRAF tools were used with academics to explore their understandings of and training needs in SRAF; central to this work was the development of a SRAF scale. We consider the value of such tools in supporting academics’ professional development needs in SRAF. The reliability and validity of the SRAF scale was tested using exploratory factor analyses (EFA). Results: Iterative EFA resulted in a 17 item support required SRAF scale (SR). Two underpinning factors: Creating the Conditions for SRAF, and Supporting Students’ SRAF Skills Development were identified. The reliability of the instrument supported its primary use as a tool to facilitate academics’ professional development in fostering students’ self-regulatory skills. Discussion: Our findings highlight the importance of supporting academics in developing strategies to maximize students’ metacognitive skills and motivation in assessment and feedback, contingent on effective assessment design. Such professional development needs to be mindful of individual and contextual factors impacting academics’ access to, and confidence and competence in, using SRAF in practice. This research is important in highlighting potential disconnects between where academics’ focus their attention in assessment, and what is known to have most impact on student learning success. The SRAF tools have considerable potential in supporting translation of theory into practice as part of sustained professional development for academics in higher education
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