Multimodal Imaging Nanoparticles Derived from Hyaluronic Acid for Integrated Preoperative and Intraoperative Cancer Imaging

Surgical resection remains the most promising treatment strategy for many types of cancer. Residual malignant tissue after surgery, a consequence in part due to positive margins, contributes to high mortality and disease recurrence. In this study, multimodal contrast agents for integrated preoperative magnetic resonance imaging (MRI) and intraoperative fluorescence image-guided surgery (FIGS) are developed. Self-assembled multimodal imaging nanoparticles (SAMINs) were developed as a mixed micelle formulation using amphiphilic HA polymers functionalized with either GdDTPA for T1 contrast-enhanced MRI or Cy7.5, a near infrared fluorophore. To evaluate the relationship between MR and fluorescence signal from SAMINs, we employed simulated surgical phantoms that are routinely used to evaluate the depth at which near infrared (NIR) imaging agents can be detected by FIGS. Finally, imaging agent efficacy was evaluated in a human breast tumor xenograft model in nude mice, which demonstrated contrast in both fluorescence and magnetic resonance imaging

Unconditional care in academic emergency departments

Recent news stories have explicitly stated that patients with symptoms of COVID-19 were "turned away" from emergency departments. This commentary addresses these serious allegations, with an attempt to provide the perspective of academic emergency departments (EDs) around the Nation. The overarching point we wish to make is that academic EDs never deny emergency care to any person

Scale-up of HIV Treatment Through PEPFAR: A Historic Public Health Achievement

Since its inception in 2003, the US President’s Emergency Plan for AIDS Relief (PEPFAR) has been an important driving force behind the global scale-up of HIV care and treatment services, particularly in expansion of access to antiretroviral therapy. Despite initial concerns about cost and feasibility, PEPFAR overcame challenges by leveraging and coordinating with other funders, by working in partnership with the most affected countries, by supporting local ownership, by using a public health approach, by supporting task-shifting strategies, and by paying attention to health systems strengthening. As of September 2011, PEPFAR directly supported initiation of antiretroviral therapy for 3.9 million people and provided care and support for nearly 13 million people. Benefits in terms of prevention of morbidity and mortality have been reaped by those receiving the services, with evidence of societal benefits beyond the anticipated clinical benefits. However, much remains to be accomplished to achieve universal access, to enhance the quality of programs, to ensure retention of patients in care, and to continue to strengthen health systems

Publisher Correction: The genome of the stable fly, Stomoxys calcitrans, reveals potential mechanisms underlying reproduction, host interactions, and novel targets for pest control (BMC Biology, (2021), 19, 1, (41), 10.1186/s12915-021-00975-9)

Following publication of the original article [1], it was reported that the article copyright was incorrect. The correct copyright statement is: © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021. The original article [1] has been corrected

Total column ozone climatology from MY34 to MY36 from measurements by the NOMAD-UVIS spectrometer

Near continuous radiance measurements of the martian atmosphere in the 200-650 nm wavelength range by the Ultraviolet and VISible spectrometer (UVIS) (Patel et al., 2017) as part of the NOMAD instrument on the ExoMars Trace Gas Orbiter (TGO) (Vandaele, et al., 2018) provides a powerful tool for investigating the ozone climatology, the water cycle (from the well established photochemical anti-correlation between water vapour and ozone), and by extension photochemical reactions in the martian atmosphere. Previous observations have shown that, spatially, ozone is observed in three main regions (1) at high northern latitudes (50° - 90° N) through the northern autumn, winter and spring seasons, (2) at equivalent high southern latitudes during the aphelion season, and (3) at low latitudes between 30°S - 30°N from Ls = 30° - 120°, coinciding with observations of the aphelion cloud belt (Bertaux et al., 2000; Clancy et al., 2016; Holmes et al., 2018). Entrapment of ozone in deep depressions, such as Hellas basin (Clancy et al., 2016), has been observed and associated with the meridional transport of O-rich air from northern latitudes and from south polar air being transported to equatorial regions after southern winter. In this study, radiative transfer modelling, that includes multiple scattering from aerosols and surface reflectance, has been used to model the UVIS radiances in the wavelength range 220-310 nm to retrieve the O3 column abundances for the latter half of Mars Year (MY)34 through MY36. We report the spatial distribution of ozone as measured by UVIS, including the observed entrapment and diurnal cycle of ozone within Hellas basin

Urban and rural prevalence of diabetes and pre- diabetes and risk factors associated with diabetes in Tanzania and Uganda

CITATION: Chiwanga, F. S., et al. 2016. Urban and rural prevalence of diabetes and pre- diabetes and risk factors associated with diabetes in Tanzania and Uganda. Global Health Action, 9(1):31440, doi:10.3402/gha.v9.31440.The original publication is available at http://www.tandfonline.comENGLISH SUMMARY : Background: The increase in prevalence of diabetes and pre-diabetes in sub-Saharan Africa underlines the importance of understanding its magnitude and causes in different population groups. We analyzed data from the Africa/Harvard Partnership for Cohort Research and Training (PaCT) studies to determine the prevalence of diabetes and pre-diabetes and risk factors associated with diabetes. Methodology: Participants were randomly selected from peri-urban (n 297) and rural (n 200) communities in Uganda, and teachers were recruited from schools (n 229) in urban Tanzania. We used a standardized questionnaire to collect socio-demographic and self-reported disease status including diabetes status. Blood glucose was also measured after participants fasted for 8 h. We used standard protocols for anthropometric and blood pressure measurement. Results: The overall prevalence of diabetes was 10.1% and was highest in rural Ugandan residents (16.1%) compared to teachers in Tanzania (8.3%) and peri-urban Ugandan residents (7.6%). The prevalence of pre-diabetes was 13.8%. The prevalence of self-reported diabetes was low across all sites, where 68% of participants with diabetes were not captured by self-report. In ultivariable logistic regression analysis, family history (OR 2.5, 95% CI: 1.1, 5.6) and hypertension (OR 2.3, 95% CI: 1.1, 5.2) were significantly associated with diabetes. Conclusions: The prevalence of diabetes and pre-diabetes in Uganda and Tanzania is high, differs markedly between population groups, and remains undiagnosed in an alarmingly high proportion of individuals. These findings highlight the need for large-scale, prospective studies to accurately quantify the burden and identify effective intervention and treatment strategies across diverse African populations.http://www.tandfonline.com/doi/full/10.3402/gha.v9.31440Publisher's versio

Proteomic Analysis of Neisseria gonorrhoeae Biofilms Shows Shift to Anaerobic Respiration and Changes in Nutrient Transport and Outermembrane Proteins

Neisseria gonorrhoeae, the causative agent of gonorrhea, can form biofilms in vitro and in vivo. In biofilms, the organism is more resistant to antibiotic treatment and can serve as a reservoir for chronic infection. We have used stable isotope labeling by amino acids in cell culture (SILAC) to compare protein expression in biofilm and planktonic organisms. Two parallel populations of N. gonorrhoeae strain 1291, which is an arginine auxotroph, were grown for 48 h in continuous-flow chambers over glass, one supplemented with 13C6-arginine for planktonic organisms and the other with unlabeled arginine for biofilm growth. The biofilm and planktonic cells were harvested and lysed separately, and fractionated into three sequential protein extracts. Corresponding heavy (H) planktonic and light (L) biofilm protein extracts were mixed and separated by 1D SDS-PAGE gels, and samples were extensively analyzed by liquid chromatography-mass spectrometry. Overall, 757 proteins were identified, and 152 unique proteins met a 1.5-fold cutoff threshold for differential expression with p-values <0.05. Comparing biofilm to planktonic organisms, this set included 73 upregulated and 54 downregulated proteins. Nearly a third of the upregulated proteins were involved in energy metabolism, with cell envelope proteins making up the next largest group. Of the downregulated proteins, the largest groups were involved in protein synthesis and energy metabolism. These proteomics results were compared with our previously reported results from transcriptional profiling of gonococcal biofilms using microarrays. Nitrite reductase and cytochrome c peroxidase, key enzymes required for anaerobic growth, were detected as highly upregulated in both the proteomic and transcriptomic datasets. These and other protein expression changes observed in the present study were consistent with a shift to anaerobic respiration in gonococcal biofilms, although changes in membrane proteins not explicitly related to this shift may have other functions

Prenatal Excess Glucocorticoid Exposure and Adult Affective Disorders:A Role for Serotonergic and Catecholamine Pathways

Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal ‘programming’ of adult affective behaviours such as depression and anxiety. Indeed, the glucocorticoid metabolising enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is highly expressed in the placenta and the developing fetus, acts as a protective barrier from the high maternal glucocorticoids which may alter developmental trajectories. The programmed changes resulting from maternal stress or bypass or from the inhibition of 11β-HSD2 are frequently associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Hence, circulating glucocorticoid levels are increased either basally or in response to stress accompanied by CNS region-specific modulations in the expression of both corticosteroid receptors (mineralocorticoid and glucocorticoid receptors). Furthermore, early-life glucocorticoid exposure also affects serotonergic and catecholamine pathways within the brain, with changes in both associated neurotransmitters and receptors. Indeed, global removal of 11β-HSD2, an enzyme that inactivates glucocorticoids, increases anxiety‐ and depressive-like behaviour in mice; however, in this case the phenotype is not accompanied by overt perturbation in the HPA axis but, intriguingly, alterations in serotonergic and catecholamine pathways are maintained in this programming model. This review addresses one of the potential adverse effects of glucocorticoid overexposure in utero, i.e. increased incidence of affective behaviours, and the mechanisms underlying these behaviours including alteration of the HPA axis and serotonergic and catecholamine pathways