Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function.

With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function

Autism Spectrum Disorder Among US Children (2002–2010): Socioeconomic, Racial, and Ethnic Disparities

Objectives. To describe the association between indicators of socioeconomic status (SES) and the prevalence of autism spectrum disorder (ASD) in the United States during the period 2002 to 2010, when overall ASD prevalence among children more than doubled, and to determine whether SES disparities account for ongoing racial and ethnic disparities in ASD prevalence

Cost-effectiveness analysis of universal human papillomavirus vaccination using a dynamic Bayesian methodology: The BEST II study

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE: The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context

Children With Autism Spectrum Disorder With Regression Exhibit a Different Profile in Plasma Cytokines and Adhesion Molecules Compared to Children Without Such Regression

In the etiopathogenesis of autism spectrum disorder (ASD), it has been suggested that a proinflammatory condition, as well as an alteration in adhesion molecules in the early stages of neurodevelopment, may play a role in the pathophysiology of the disorder. This study set out to evaluate the plasma levels of certain inflammatory cytokines, adhesion molecules, and growth factors in a sample of pediatric patients with ASD and compare them to the levels in a control group of healthy children. Higher levels of NGF were observed in the ASD group compared with the levels in the control group (p < 0.05). However, in the analysis of the ASD subgroups, lower plasma levels of NCAM and higher levels of NGF were found in the group of ASD children without developmental regression compared to the levels in the group of typically-developing children. These results suggest differences that could be related to different pathophysiological mechanisms in ASD. There is not a specific profile for the expression of relevant plasma cytokines, adhesion molecules or growth factors in children with ASD compared with that in typically-developing children. However, in the ANMR and AMR subgroups, some of the adhesion molecules and neuronal growth factors show differences that may be related to synaptogenesisThis study was supported by the FUNDACIÓ AGRUPACIÓ Àmbit de la Infància, 404 Research Grant INVEST from the Spanish Society of Pediatrics and Red de Salud Materno Infantil (RED SAMID)

Cost-effectiveness and affordability of community mobilisation through women's groups and quality improvement in health facilities (MaiKhanda trial) in Malawi.

Understanding the cost-effectiveness and affordability of interventions to reduce maternal and newborn deaths is critical to persuading policymakers and donors to implement at scale. The effectiveness of community mobilisation through women's groups and health facility quality improvement, both aiming to reduce maternal and neonatal mortality, was assessed by a cluster randomised controlled trial conducted in rural Malawi in 2008-2010. In this paper, we calculate intervention cost-effectiveness and model the affordability of the interventions at scale

GPCR Genes as Activators of Surface Colonization Pathways in a Model Marine Diatom

Publisher's version (útgefin grein)Surface colonization allows diatoms, a dominant group of phytoplankton in oceans, to adapt to harsh marine environments while mediating biofoulings to human-made underwater facilities. The regulatory pathways underlying diatom surface colonization, which involves morphotype switching in some species, remain mostly unknown. Here, we describe the identification of 61 signaling genes, including G-protein-coupled receptors (GPCRs) and protein kinases, which are differentially regulated during surface colonization in the model diatom species, Phaeodactylum tricornutum. We show that the transformation of P. tricornutum with constructs expressing individual GPCR genes induces cells to adopt the surface colonization morphology. P. tricornutum cells transformed to express GPCR1A display 30% more resistance to UV light exposure than their non-biofouling wild-type counterparts, consistent with increased silicification of cell walls associated with the oval biofouling morphotype. Our results provide a mechanistic definition of morphological shifts during surface colonization and identify candidate target proteins for the screening of eco-friendly, anti-biofouling molecules.Financial support for this work was provided by New York University Abu Dhabi Faculty Research Funds ( AD060 ) and NYUAD Institute grant ( 73 71210 CGSB9 ). W.F. was additionally supported by the Icelandic Technology Development Fund ( 163922-0611 ). The authors thank Kenan S. Jijakli and Joseph Koussa for editing and comments on the generation of several figures. We thank the NYU Abu Dhabi Core Technology Platforms (CTP) and NYUAD Bioinformatics Core for assistance. We thank Marc Arnoux and Nizar Drou for help with high throughput sequencing and analysis.Peer Reviewe

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700