Inertio-elastic focusing of bioparticles in microchannels at high throughput

Controlled manipulation of particles from very large volumes of fluid at high throughput is critical for many biomedical, environmental and industrial applications. One promising approach is to use microfluidic technologies that rely on fluid inertia or elasticity to drive lateral migration of particles to stable equilibrium positions in a microchannel. Here, we report on a hydrodynamic approach that enables deterministic focusing of beads, mammalian cells and anisotropic hydrogel particles in a microchannel at extremely high flow rates. We show that on addition of micromolar concentrations of hyaluronic acid, the resulting fluid viscoelasticity can be used to control the focal position of particles at Reynolds numbers up to Re≈10,000 with corresponding flow rates and particle velocities up to 50 ml min[superscript −1] and 130 m s[superscript −1]. This study explores a previously unattained regime of inertio-elastic fluid flow and demonstrates bioparticle focusing at flow rates that are the highest yet achieved.National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41 BioMicroElectroMechanical Systems Resource Center)National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41 EB002503)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Army Research Office (Institute for Collaborative Biotechnologies Grant W911NF-09-0001

Facilitators and barriers to adolescent participation in a TB clinical trial.

BACKGROUNDThe inclusion of adolescents in TB drug trials is essential for the development of safe, child-friendly regimens for the prevention and treatment of TB. TB Trials Consortium Study 31/AIDS Clinical Trials Group A5349 (S31/A5349) enrolled adolescents as young as 12 years old. We assessed investigator and coordinator described facilitators and barriers to adolescent recruitment, enrollment, and retention.METHODSInterviews were conducted with six investigators from sites that enrolled adolescent participants and six investigators from non-enrolling sites. Additionally, two focus groups were conducted with study coordinators from enrolling sites and two focus groups with non-enrolling sites. Discussions were transcribed, analyzed, summarized, and summaries were reviewed by Community Research Advisors Group members and research group representatives for content validity.RESULTSInvestigators and coordinators attributed the successful enrollment of adolescents to the establishment and cultivation of external partnerships, flexibility to accommodate adolescents' schedules, staff engagement, recruitment from multiple locations, dedicated recruitment staff working onsite to access potential participants, creation of youth-friendly environments, and effective communications. Non-enrolling sites were mainly hindered by regulations. Suggestions for improvement in future trials focused on study planning and site preparations.CONCLUSIONProactive partnerships and collaboration with institutions serving adolescents helped identify and reduce barriers to their inclusion in this trial.

Does a competitive voucher program for adolescents improve the quality of reproductive health care? A simulated patient study in Nicaragua

BACKGROUND: Little is known about how sexual and reproductive (SRH) health can be made accessible and appropriate to adolescents. This study evaluates the impact and sustainability of a competitive voucher program on the quality of SRH care for poor and underserved female adolescents and the usefulness of the simulated patient (SP) method for such evaluation. METHODS: 28,711 vouchers were distributed to adolescents in disadvantaged areas of Managua that gave free-of-charge access to SRH care in 4 public, 10 non-governmental and 5 private clinics. Providers received training and guidelines, treatment protocols, and financial incentives for each adolescent attended. All clinics were visited by female adolescent SPs requesting contraception. SPs were sent one week before, during (with voucher) and one month after the intervention. After each consultation they were interviewed with a standardized questionnaire. Twenty-one criteria were scored and grouped into four categories. Clinics' scores were compared using non-parametric statistical methods (paired design: before-during and before-after). Also the influence of doctors' characteristics was tested using non-parametric statistical methods. RESULTS: Some aspects of service quality improved during the voucher program. Before the program started 8 of the 16 SPs returned 'empty handed', although all were eligible contraceptive users. During the program 16/17 left with a contraceptive method (p = 0.01). Furthermore, more SPs were involved in the contraceptive method choice (13/17 vs.5/16, p = 0.02). Shared decision-making on contraceptive method as well as condom promotion had significantly increased after the program ended. Female doctors had best scores before- during and after the intervention. The improvements were more pronounced among male doctors and doctors older than 40, though these improvements did not sustain after the program ended. CONCLUSION: This study illustrates provider-related obstacles adolescents often face when requesting contraception. The care provided during the voucher program improved for some important outcomes. The improvements were more pronounced among providers with the weakest initial performance. Shared decision-making and condom promotion were improvements that sustained after the program ended. The SP method is suitable and relatively easy to apply in monitoring clinics' performance, yielding important and relevant information. Objective assessment of change through the SP method is much more complex and expensive

The links between health-related behaviors and life satisfaction in elderly individuals who prefer institutional living

BACKGROUND: Life satisfaction among residents of institutions is becoming an important issue in a rapidly aging population. The aim of this cross-sectional study was to investigate the links between life satisfaction and health-related behaviors amongst functionally independent elderly people who prefer institutional living in İstanbul, Turkey. METHODS: The socio-demographic characteristics, health-related behaviors, leisure-time activities and fall histories of 133 residents of an institution in Istanbul were assessed by a structured questionnaire during face-to-face interviews. A validated life-satisfaction index questionnaire (LSI-A) was completed. RESULTS: The mean age of the study group was 73.9 ± 8.0 (range 60–90 years). Within the group, 22.6% had never married and 14.3% had university degrees. The majority (71.4%) were in the low income bracket. The overall mean LSI-A score was 20.3 ± 5.9. Participants who declared moderate/high income levels had a significantly higher mean LSI-A score than those in the low-income bracket (p = 0.009). Multivariate analysis of the data suggested that leisure-time activities and participation in regular physical activities are significant predictors of LSI-A scores (R(2): 0.112; p = 0.005 and p = 0.02, respectively). CONCLUSION: The findings imply that regular physical activity and leisure-time activities are significantly related to life satisfaction among residents in institutions. Participation in physical activity and leisure-time activity programs may help to improve the life satisfaction of elderly people living in institutions

Ancestry of the Iban Is Predominantly Southeast Asian: Genetic Evidence from Autosomal, Mitochondrial, and Y Chromosomes

Humans reached present-day Island Southeast Asia (ISEA) in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that south-to-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry. Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-to-south migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP) markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y (NRY) and mitochondrial (mt) DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data

Detection of Light Images by Simple Tissues as Visualized by Photosensitized Magnetic Resonance Imaging

In this study, we show how light can be absorbed by the body of a living rat due to an injected pigment circulating in the blood stream. This process is then physiologically translated in the tissue into a chemical signature that can be perceived as an image by magnetic resonance imaging (MRI). We previously reported that illumination of an injected photosynthetic bacteriochlorophyll-derived pigment leads to a generation of reactive oxygen species, upon oxygen consumption in the blood stream. Consequently, paramagnetic deoxyhemoglobin accumulating in the illuminated area induces changes in image contrast, detectable by a Blood Oxygen Level Dependent (BOLD)-MRI protocol, termed photosensitized (ps)MRI. Here, we show that laser beam pulses synchronously trigger BOLD-contrast transients in the tissue, allowing representation of the luminous spatiotemporal profile, as a contrast map, on the MR monitor. Regions with enhanced BOLD-contrast (7-61 fold) were deduced as illuminated, and were found to overlap with the anatomical location of the incident light. Thus, we conclude that luminous information can be captured and translated by typical oxygen exchange processes in the blood of ordinary tissues, and made visible by psMRI (Fig. 1). This process represents a new channel for communicating environmental light into the body in certain analogy to light absorption by visual pigments in the retina where image perception takes place in the central nervous system. Potential applications of this finding may include: non-invasive intra-operative light guidance and follow-up of photodynamic interventions, determination of light diffusion in opaque tissues for optical imaging and possible assistance to the blind

Natural Cross Chlamydial Infection between Livestock and Free-Living Bird Species

The study of cross-species pathogen transmission is essential to understanding the epizootiology and epidemiology of infectious diseases. Avian chlamydiosis is a zoonotic disease whose effects have been mainly investigated in humans, poultry and pet birds. It has been suggested that wild bird species play an important role as reservoirs for this disease. During a comparative health status survey in common (Falco tinnunculus) and lesser (Falco naumanni) kestrel populations in Spain, acute gammapathies were detected. We investigated whether gammapathies were associated with Chlamydiaceae infections. We recorded the prevalence of different Chlamydiaceae species in nestlings of both kestrel species in three different study areas. Chlamydophila psittaci serovar I (or Chlamydophila abortus), an ovine pathogen causing late-term abortions, was isolated from all the nestlings of both kestrel species in one of the three studied areas, a location with extensive ovine livestock enzootic of this atypical bacteria and where gammapathies were recorded. Serovar and genetic cluster analysis of the kestrel isolates from this area showed serovars A and C and the genetic cluster 1 and were different than those isolated from the other two areas. The serovar I in this area was also isolated from sheep abortions, sheep faeces, sheep stable dust, nest dust of both kestrel species, carrion beetles (Silphidae) and Orthoptera. This fact was not observed in other areas. In addition, we found kestrels to be infected by Chlamydia suis and Chlamydia muridarum, the first time these have been detected in birds. Our study evidences a pathogen transmission from ruminants to birds, highlighting the importance of this potential and unexplored mechanism of infection in an ecological context. On the other hand, it is reported a pathogen transmission from livestock to wildlife, revealing new and scarcely investigated anthropogenic threats for wild and endangered species

Citalopram reduces aggregation of ATXN3 in a YAC transgenic mouse model of Machado-Joseph disease

Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is a fatal polyglutamine disease with no disease-modifying treatment. The selective serotonin reuptake inhibitor citalopram was shown in nematode and mouse models to be a compelling repurposing candidate for Machado-Joseph disease therapeutics. We sought to confirm the efficacy of citalopram to decrease ATXN3 aggregation in an unrelated mouse model of Machado-Joseph disease. Four-week-old YACMJD84.2 mice and non-transgenic littermates were given citalopram 8 mg/kg in drinking water or water for 10 weeks. At the end of treatment, brains were collected for biochemical and pathological analyses. Brains of citalopram-treated YACMJD84.2 mice showed an approximate 50% decrease in the percentage of cells containing ATXN3-positive inclusions in the substantia nigra and three examined brainstem nuclei compared to controls. No differences in ATXN3 inclusion load were observed in deep cerebellar nuclei of mice. Citalopram effect on ATXN3 aggregate burden was corroborated by immunoblotting analysis. While lysates from the brainstem and cervical spinal cord of citalopram-treated mice showed a decrease in all soluble forms of ATXN3 and a trend toward reduction of insoluble ATXN3, no differences in ATXN3 levels were found between cerebella of citalopram-treated and vehicle-treated mice. Citalopram treatment altered levels of select components of the cellular protein homeostatic machinery that may be expected to enhance the capacity to refold and/or degrade mutant ATXN3. The results here obtained in a second independent mouse model of Machado-Joseph disease further support citalopram as a potential drug to be repurposed for this fatal disorder.This work was funded by Becky Babcox Research Fund/pilot research award G015617, University of Michigan to M.C.C. and NINDS/NIH R01NS038712 to H.L.P. The work performed at the University of Minho was funded by the European Regional Development Funds (FEDER), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER. This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to P.M.) and [EXPL/BIM-MEC/ 0239/2012] (to A.T.C.); by FCT through the project [POCI-01-0145- FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to P.M.); by National Ataxia Foundation (to P.M. and to A.T.C.); and by Ataxia UK (to P.M.). S.D.S. and A.T.C. were supported by fellowships from FCT, SFRH/BD/ 78388/2011 and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa and EU/FSE

Ethnic-Racial Socialization in Early Childhood: The Implications of Color-Consciousness and Colorblindness for Prejudice Development

This chapter outlines how early childhood teachers can bring children into conversations surrounding race and racism by drawing on literature on how parents of color discuss these topics. Although educators’ practices surrounding race and racism remain largely unexplored, decades of developmental psychological research indicate that parents of color engage in ethnic-racial socialization practices that are beneficial for children (Hughes et al., 2006). The established dimensions of parental ethnic-racial socialization include (1) cultural socialization, or teaching children about their ethnic heritage and instilling ethnic pride; (2) preparation for bias, or teaching children about racism and preparing them to face discrimination; (3) promotion of mistrust, or warning children about the need to distance themselves from other racial groups; and (4) egalitarianism, or emphasizing the similarities between and equality of all races (Hughes et al. 2006). One consideration to take into account from a developmental perspective is that children’s level of cognitive development impacts how they interpret messages about race. This chapter draws a link between parental ethnic-racial socialization and extends this body of work to school settings, with a focus on teachers. The ideologies of colorblindness and color-consciousness are discussed throughout