Elevation of gangliosides in four brain regions from Parkinson’s disease patients with a GBA mutation

A number of genetic risk factors have been identified over the past decade for Parkinson's Disease (PD), with variants in GBA prominent among them. GBA encodes the lysosomal enzyme that degrades the glycosphingolipid, glucosylceramide (GlcCer), with the activity of this enzyme defective in Gaucher disease. Based on the ill-defined relationship between glycosphingolipid metabolism and PD, we now analyze levels of various lipids by liquid chromatography/electrospray ionization-tandem mass spectrometry in four brain regions from age- and sex-matched patient samples, including idiopathic PD, PD patients with a GBA mutation and compare both to control brains (n = 21 for each group) obtained from individuals who died from a cause unrelated to PD. Of all the glycerolipids, sterols, and (glyco)sphingolipids (251 lipids in total), the only lipid class which showed significant differences were the gangliosides (sialic acid-containing complex glycosphingolipids), which were elevated in 3 of the 4 PD-GBA brain regions. There was no clear correlation between levels of individual gangliosides and the genetic variant in Gaucher disease [9 samples of severe (neuronopathic), 4 samples of mild (non-neuronopathic) GBA variants, and 8 samples with low pathogenicity variants which have a higher risk for development of PD]. Most brain regions, i.e. occipital cortex, cingulate gyrus, and striatum, did not show a statistically significant elevation of GlcCer in PD-GBA. Only one region, the middle temporal gyrus, showed a small, but significant elevation in GlcCer concentration in PD-GBA. We conclude that changes in ganglioside, but not in GlcCer levels, may contribute to the association between PD and GBA mutations

Surgical need among the ageing population of Uganda

Background: Uganda’s ageing population (age 50 years and older) will nearly double from 2015 to 2050. HIV/AIDS, diabetes, stroke among other disease processes have been studied in the elderly population. However, the burden of disease from surgi- cally-treatable conditions is unknown. Objectives: To determine the proportion of adults above 50 years with unmet surgical need and deaths attributable to probable surgically-treatable conditions. Methods: A cluster randomized sample representing the national population of Uganda was enumerated. The previously vali- dated Surgeons Overseas assessment of surgical need instrument, a head-to-toe verbal interview, was used to determine any sur- gically-treatable conditions in two randomly-selected living household members. Deaths were detailed by heads of households. Weighted metrics are calculated taking sampling design into consideration and Taylor series linearization was used for sampling error estimation.   Results: The study enumerated 425 individuals above age 50 years. The prevalence proportion of unmet surgical need was 27.8% (95%CI, 22.1-34.3). This extrapolates to 694,722 (95%CI, 552,279-857,157) individuals living with one or more surgically treatable conditions. The North sub-region was observed to have the highest prevalence proportion. Nearly two out of five household deaths (37.9%) were attributed to probable surgically treatable causes.Conclusion: There is disproportionately high need for surgical care among the ageing population of Uganda with approximate- ly 700,000 consultations needed.Keywords: Surgical need, ageing population, Uganda

Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival

The regulation of pancreatic β cell mass is a critical factor to help maintain normoglycemia during insulin resistance. Nutrient-sensing G protein-coupled receptors (GPCR) contribute to aspects of β cell function, including regulation of β cell mass. Nutrients such as free fatty acids (FFAs) contribute to precise regulation of β cell mass by signaling through cognate GPCRs, and considerable evidence suggests that circulating FFAs promote β cell expansion by direct and indirect mechanisms. Free Fatty Acid Receptor 2 (FFA2) is a β cell-expressed GPCR that is activated by short chain fatty acids, particularly acetate. Recent studies of FFA2 suggest that it may act as a regulator of β cell function. Here, we set out to explore what role FFA2 may play in regulation of β cell mass. Interestingly, Ffar2(-/-) mice exhibit diminished β cell mass at birth and throughout adulthood, and increased β cell death at adolescent time points, suggesting a role for FFA2 in establishment and maintenance of β cell mass. Additionally, activation of FFA2 with Gαq/11-biased agonists substantially increased β cell proliferation in in vitro and ex vivo proliferation assays. Collectively, these data suggest that FFA2 may be a novel therapeutic target to stimulate β cell growth and proliferation

The bolometric focal plane array of the Polarbear CMB experiment

The Polarbear Cosmic Microwave Background (CMB) polarization experiment is currently observing from the Atacama Desert in Northern Chile. It will characterize the expected B-mode polarization due to gravitational lensing of the CMB, and search for the possible B-mode signature of inflationary gravitational waves. Its 250 mK focal plane detector array consists of 1,274 polarization-sensitive antenna-coupled bolometers, each with an associated lithographed band-defining filter. Each detector's planar antenna structure is coupled to the telescope's optical system through a contacting dielectric lenslet, an architecture unique in current CMB experiments. We present the initial characterization of this focal plane

Ultra High Energy Cosmology with POLARBEAR

Observations of the temperature anisotropy of the Cosmic Microwave Background (CMB) lend support to an inflationary origin of the universe, yet no direct evidence verifying inflation exists. Many current experiments are focussing on the CMB's polarization anisotropy, specifically its curl component (called "B-mode" polarization), which remains undetected. The inflationary paradigm predicts the existence of a primordial gravitational wave background that imprints a unique B-mode signature on the CMB's polarization at large angular scales. The CMB B-mode signal also encodes gravitational lensing information at smaller angular scales, bearing the imprint of cosmological large scale structures (LSS) which in turn may elucidate the properties of cosmological neutrinos. The quest for detection of these signals; each of which is orders of magnitude smaller than the CMB temperature anisotropy signal, has motivated the development of background-limited detectors with precise control of systematic effects. The POLARBEAR experiment is designed to perform a deep search for the signature of gravitational waves from inflation and to characterize lensing of the CMB by LSS. POLARBEAR is a 3.5 meter ground-based telescope with 3.8 arcminute angular resolution at 150 GHz. At the heart of the POLARBEAR receiver is an array featuring 1274 antenna-coupled superconducting transition edge sensor (TES) bolometers cooled to 0.25 Kelvin. POLARBEAR is designed to reach a tensor-to-scalar ratio of 0.025 after two years of observation -- more than an order of magnitude improvement over the current best results, which would test physics at energies near the GUT scale. POLARBEAR had an engineering run in the Inyo Mountains of Eastern California in 2010 and will begin observations in the Atacama Desert in Chile in 2011.Comment: 8 pages, 6 figures, DPF 2011 conference proceeding

GM-CSF Increases Mucosal and Systemic Immunogenicity of an H1N1 Influenza DNA Vaccine Administered into the Epidermis of Non-Human Primates

Background: The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a worldwide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99) HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun) was analyzed in rhesus macaques. Methodology/Principal Findings: Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particlemediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI) antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine. Conclusions/Significance: These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skindelivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract. © 2010 Loudon et al

AMI Large Array radio continuum observations of Spitzer c2d small clouds and cores

We perform deep 1.8 cm radio continuum imaging towards thirteen protostellar regions selected from the Spitzer c2d small clouds and cores programme at high resolution (25") in order to detect and quantify the cm-wave emission from deeply embedded young protostars. Within these regions we detect fifteen compact radio sources which we identify as radio protostars including two probable new detections. The sample is in general of low bolometric luminosity and contains several of the newly detected VeLLO sources. We determine the 1.8 cm radio luminosity to bolometric luminosity correlation, L_rad -L_bol, for the sample and discuss the nature of the radio emission in terms of the available sources of ionized gas. We also investigate the L_rad-L_IR correlation and suggest that radio flux density may be used as a proxy for the internal luminosity of low luminosity protostars.Comment: submitted MNRA

Optimizing Care for Ugandans with Untreated Abdominal Surgical Conditions

Background: Abdominal operations account for a majority of surgical volume in low-income countries, yet population-level prevalence data on surgically treatable abdominal conditions are scarce. Objective: In this study, our objective was to quantify the burden of surgically treatable abdominal conditions in Uganda. Methods: In 2014, we administered a two-stage cluster-randomized Surgeons OverSeas Assessment of Surgical Need survey to 4,248 individuals in 105 randomly selected clusters (representing the national population of Uganda). Findings: Of the 4,248 respondents, 185 reported at least one surgically treatable abdominal condition in their lifetime, giving an estimated lifetime prevalence of 3.7% (95% CI: 3.0 to 4.6%). Of those 185 respondents, 76 reported an untreated condition, giving an untreated prevalence of 1.7% (95% CI: 1.3 to 2.3%). Obstructed labor (52.9%) accounted for most of the 238 abdominal conditions reported and was untreated in only 5.6% of reported conditions. In contrast, 73.3% of reported abdominal masses were untreated. Conclusions: Individuals in Uganda with nonobstetric abdominal surgical conditions are disproportionately undertreated. Major health system investments in obstetric surgical capacity have been beneficial, but our data suggest that further investments should aim at matching overall surgical care capacity with surgical need, rather than focusing on a single operation for obstructed labor

Surgical need among the ageing population of Uganda

Background: Uganda\u2019s ageing population (age 50 years and older) will nearly double from 2015 to 2050. HIV/AIDS, diabetes, stroke among other disease processes have been studied in the elderly population. However, the burden of disease from surgically-treatable conditions is unknown. Objectives: To determine the proportion of adults above 50 years with unmet surgical need and deaths attributable to probable surgically-treatable conditions. Methods: A cluster randomized sample representing the national population of Uganda was enumerated. The previously validated Surgeons Overseas assessment of surgical need instrument, a head-to-toe verbal interview, was used to determine any surgically-treatable conditions in two randomly-selected living household members. Deaths were detailed by heads of households. Weighted metrics are calculated taking sampling design into consideration and Taylor series linearization was used for sampling error estimation. Results: The study enumerated 425 individuals above age 50 years. The prevalence proportion of unmet surgical need was 27.8% (95%CI, 22.1-34.3). This extrapolates to 694,722 (95%CI, 552,279-857,157) individuals living with one or more surgically treatable conditions. The North sub-region was observed to have the highest prevalence proportion. Nearly two out of five household deaths (37.9%) were attributed to probable surgically treatable causes. Conclusion: There is disproportionately high need for surgical care among the ageing population of Uganda with approximately 700,000 consultations needed. DOI: https://dx.doi.org/10.4314/ahs.v19i1.54 Cite as: Tran TM, Fuller AT, Butler EK, Muhumuza C, Ssennono VF, Vissoci JR, et al. Surgical need among the ageing population of Uganda. Afri Health Sci. 2019;19(1). 1778-1788. https:// dx.doi. org/10.4314/ ahs. v19i1.5

SN2019dge: a Helium-rich Ultra-Stripped Envelope Supernova

We present observations of ZTF18abfcmjw (SN2019dge), a helium-rich supernova with a fast-evolving light curve indicating an extremely low ejecta mass (≈0.33 M_⊙) and low kinetic energy (≈1.3 × 10⁵⁰ erg). Early-time (<4 days after explosion) photometry reveals evidence of shock cooling from an extended helium-rich envelope of ~0.1 M_⊙ located ~1.2 × 10¹³ cm from the progenitor. Early-time He II line emission and subsequent spectra show signatures of interaction with helium-rich circumstellar material, which extends from ≳ 5 × 10¹³ cm to 2 × 10¹⁶ cm. We interpret SN2019dge as a helium-rich supernova from an ultra-stripped progenitor, which originates from a close binary system consisting of a mass-losing helium star and a low-mass main-sequence star or a compact object (i.e., a white dwarf, a neutron star, or a black hole). We infer that the local volumetric birth rate of 19dge-like ultra-stripped SNe is in the range of 1400–8200 Gpc⁻³ yr⁻¹ (i.e., 2%–12% of core-collapse supernova rate). This can be compared to the observed coalescence rate of compact neutron star binaries that are not formed by dynamical capture