The effect of calcitriol, paricalcitol, and a calcimimetic on extraosseous calcifications in uremic rats

Vitamin D derivatives and calcimimetics are used to treat secondary hyperparathyroidism in patients with chronic renal failure. We investigated the effect of calcitriol, paricalcitol, and the calcimimetic AMG 641 on soft-tissue calcification in uremic rats with secondary hyperparathyroidism. Control and uremic rats were treated with vehicle, calcitriol, paricalcitol, AMG 641, or a combination of AMG 641 plus calcitriol or paricalcitol. Parathyroid hormone levels were reduced by all treatments but were better controlled by the combination of paricalcitol and AMG 641. The calcimimetic alone did not induce extraosseous calcification but co-administration of AMG 641 reduced soft-tissue calcification and aortic mineralization in both calcitriol- and paricalcitol-treated rats. Survival was significantly reduced in rats treated with calcitriol and this mortality was attenuated by co-treatment with AMG 641. Our study shows that extraskeletal calcification was present in animals treated with calcitriol and paricalcitol but not with AMG 641. When used in combination with paricalcitol, AMG 641 provided excellent control of secondary hyperparathyroidism and prevented mortality associated with the use of vitamin D derivatives without causing tissue calcification

Rapid Assessment of Insect Fragments in Flour Milled from Wheat Infested with Known Densities of Immature and Adult \u3ci\u3eSitophilus oryzae\u3c/i\u3e (Coleoptera: Curculionidae)

Milling wheat, Triticum aestivum L., infested with low densities of internal feeding insects can result in flour containing insect fragments. The Food and Drug Administration (FDA) enforces a standard or defect action level stating that a maximum of 75 insect fragments per 50 g of flour is allowed. However, the relationship between level of infestation and number of resulting fragments is not well documented, and a more rapid method for enumerating insect fragments is needed. We characterized the number of insect fragments produced from milling small lots of wheat spiked with known densities and life stages of Sitophilus oryzae (L.) (Coleoptera: Curculionidae). Insect fragments were enumerated with near-infrared spectroscopy (NIRS), a quick nondestructive procedure, and with the industry standard flotation method. Results showed that an individual small larva, large larva, pupa, or adult produced 0.4, 0.7, 1.5, and 27.0 fragments, respectively. NIRS-predicted counts of ≤51 (from small larvae), ≤53 (from large larvae), ≤43 (from pupae), or 0 (from adults) indicated that there weresample, because the upper bound of associated 95% inverse prediction confidence intervals was less than the standard; NIRS-predicted counts of ≥98, ≥117, ≥108, or ≥225 fragments (same life stages as above) signaled that these flour samples contained \u3e75 actual fragments. These data suggest that NIRS could be adopted for rapid assessment of insect fragments resulting from relatively low levels of infestation with immature life states, but that it was not accurate enough for enumerating insect fragments, relevant to FDA standards, resulting from adults

Scoping review of measures of treatment burden in patients with multimorbidity: advancements and current gaps

Objectives: To identify, assess, and summarize the measures to assess burden of treatment in patients with multimorbidity (BoT-MMs) and their measurement properties. Study Design and Setting: MEDLINE via PubMed was searched from inception until May 2021. Independent reviewers extracted data from studies in which BoT-MMs were developed, validated, or reported as used, including an assessment of their measurement properties (e.g., validity and reliability) using the COnsensus-based Standards for the selection of health Measurement INstruments. Results: Eight BoT-MMs were identified across 72 studies. Most studies were performed in English (68%), in high-income countries (90%), without noting urban-rural settings (90%). No BoT-MMs had both sufficient content validity and internal consistency; some measurement properties were either insufficient or uncertain (e.g., responsiveness). Other frequent limitations of BoT-MMs included absent recall time, presence of floor effects, and unclear rationale for categorizing and interpreting raw scores. Conclusion: The evidence needed for use of extant BoT-MMs in patients with multimorbidity remains insufficiently developed, including that of suitability for their development, measurement properties, interpretability of scores, and use in low-resource settings. This review summarizes this evidence and identifies issues needing attention for using BoT-MMs in research and clinical practice

Imprints of galaxy evolution on H ii regions Memory of the past uncovered by the CALIFA survey

H ii regions in galaxies are the sites of star formation and thus particular places to understand the build-up of stellar mass in the universe. The line ratios of this ionized gas are frequently used to characterize the ionization conditions. We use the Hii regions catalogue from the CALIFA survey (~5000 H ii regions), to explore their distribution across the classical [OIII]/Hbeta vs. [NII]/Halpha diagnostic diagram, and how it depends on the oxygen abundance, ionization parameter, electron density, and dust attenuation. We compared the line ratios with predictions from photoionization models. Finally, we explore the dependences on the properties of the host galaxies, the location within those galaxies and the properties of the underlying stellar population. We found that the location within the BPT diagrams is not totally predicted by photoionization models. Indeed, it depends on the properties of the host galaxies, their galactocentric distances and the properties of the underlying stellar population. These results indicate that although H ii regions are short lived events, they are affected by the total underlying stellar population. One may say that H ii regions keep a memory of the stellar evolution and chemical enrichment that have left an imprint on the both the ionizing stellar population and the ionized gasComment: 18 pages, 8 figures, accepted for publishing in A&

Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer

<p>Abstract</p> <p>Background</p> <p>The intensity of the inflammation induced by <it>Helicobacter pylori </it>colonization is associated with the development of distal gastric cancer (GC). The host response to <it>H</it>. <it>pylori </it>has been related to genetic polymorphisms that influence both innate and adaptive immune responses.</p> <p>Our aim was to investigate whether the presence of the <it>TLR4 Asp299Gly</it>, <it>TLR4 Thr399Ile </it>and <it>IL-8-251 </it>A/T polymorphisms had any influence in the development of distal GC in a Mexican population.</p> <p>Methods</p> <p>We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of <it>H. pylori </it>in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for <it>TLR4 Asp299Gly </it>polymorphism by pyrosequencing, for <it>TLR4 Thr399Ile </it>by PCR-RFLP and for <it>IL8-251 </it>by the amplification refractory mutation system (ARMS)-PCR.</p> <p>Results</p> <p>The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square _H-W= 0.58 for <it>IL8-251</it>, 0.42 for <it>TLR4 Asp299Gly </it>and 0.17 for <it>TLR4 Thr399Ile</it>). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for <it>TLR4- Asp299Gly </it>[the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82)] and for <it>TLR4 Thr399Ile </it>[the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for <it>IL-8-251 </it>A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1–4.2) (p = 0.023).</p> <p>Conclusion</p> <p>This study showed that the <it>IL8-251*A </it>allele could be related to the development of distal gastric cancer in this Mexican population.</p

An Innovative AI-based primer design tool for precise and accurate detection of SARS-CoV-2 variants of concern

As the COVID-19 pandemic winds down, it leaves behind the serious concern that future, even more disruptive pandemics may eventually surface. One of the crucial steps in handling the SARS-CoV-2 pandemic was being able to detect the presence of the virus in an accurate and timely manner, to then develop policies counteracting the spread. Nevertheless, as the pandemic evolved, new variants with potentially dangerous mutations appeared. Faced by these developments, it becomes clear that there is a need for fast and reliable techniques to create highly specific molecular tests, able to uniquely identify VOCs. Using an automated pipeline built around evolutionary algorithms, we designed primer sets for SARS-CoV-2 (main lineage) and for VOC, B.1.1.7 (Alpha) and B.1.1.529 (Omicron). Starting from sequences openly available in the GISAID repository, our pipeline was able to deliver the primer sets for the main lineage and each variant in a matter of hours. Preliminary in-silico validation showed that the sequences in the primer sets featured high accuracy. A pilot test in a laboratory setting confirmed the results: the developed primers were favorably compared against existing commercial versions for the main lineage, and the specific versions for the VOCs B.1.1.7 and B.1.1.529 were clinically tested successfully

Stellar Population gradients in galaxy discs from the CALIFA survey

While studies of gas-phase metallicity gradients in disc galaxies are common, very little has been done in the acquisition of stellar abundance gradients in the same regions. We present here a comparative study of the stellar metallicity and age distributions in a sample of 62 nearly face-on, spiral galaxies with and without bars, using data from the CALIFA survey. We measure the slopes of the gradients and study their relation with other properties of the galaxies. We find that the mean stellar age and metallicity gradients in the disc are shallow and negative. Furthermore, when normalized to the effective radius of the disc, the slope of the stellar population gradients does not correlate with the mass or with the morphological type of the galaxies. Contrary to this, the values of both age and metallicity at $\sim$2.5 scale-lengths correlate with the central velocity dispersion in a similar manner to the central values of the bulges, although bulges show, on average, older ages and higher metallicities than the discs. One of the goals of the present paper is to test the theoretical prediction that non-linear coupling between the bar and the spiral arms is an efficient mechanism for producing radial migrations across significant distances within discs. The process of radial migration should flatten the stellar metallicity gradient with time and, therefore, we would expect flatter stellar metallicity gradients in barred galaxies. However, we do not find any difference in the metallicity or age gradients in galaxies with without bars. We discuss possible scenarios that can lead to this absence of difference.Comment: 24 pages, 17 figures, accepted for publication in A&

Infrared spectroscopy of NGC 1068: Probing the obscured ionizing AGN continuum

The ISO-SWS 2.5-45 um infrared spectroscopic observations of the nucleus of the Seyfert 2 galaxy NGC 1068 (see companion paper) are combined with a compilation of UV to IR narrow emission line data to determine the spectral energy distribution (SED) of the obscured extreme-UV continuum that photoionizes the narrow line emitting gas in the active galactic nucleus. We search a large grid of gas cloud models and SEDs for the combination that best reproduces the observed line fluxes and NLR geometry. Our best fit model reproduces the observed line fluxes to better than a factor of 2 on average and is in general agreement with the observed NLR geometry. It has two gas components that are consistent with a clumpy distribution of dense outflowing gas in the center and a more extended distribution of less dense and more clumpy gas farther out that has no net outflow. The best fit SED has a deep trough at ~4 Ryd, which is consistent with an intrinsic Big Blue Bump that is partially absorbed by ~6x10^19 cm^-2 of neutral hydrogen interior to the NLR.Comment: 15 pp, 4 figures, ApJ accepte

Comparison of emissions from on-road sources using a mobile laboratory under various driving and operational sampling modes

Mobile sources produce a significant fraction of the total anthropogenic emissions burden in large cities and have harmful effects on air quality at multiple spatial scales. Mobile emissions are intrinsically difficult to estimate due to the large number of parameters affecting the emissions variability within and across vehicles types. The MCMA-2003 Campaign in Mexico City has showed the utility of using a mobile laboratory to sample and characterize specific classes of motor vehicles to better quantify their emissions characteristics as a function of their driving cycles. The technique clearly identifies "high emitter" vehicles via individual exhaust plumes, and also provides fleet average emission rates. We have applied this technique to Mexicali during the Border Ozone Reduction and Air Quality Improvement Program (BORAQIP) for the Mexicali-Imperial Valley in 2005. We analyze the variability of measured emission ratios for emitted NOx [NO subscript x], CO, specific VOCs, NH3 [NH subscript 3], and some primary fine particle components and properties by deploying a mobile laboratory in roadside stationary sampling, chase and fleet average operational sampling modes. The measurements reflect various driving modes characteristic of the urban fleets. The observed variability for all measured gases and particle emission ratios is greater for the chase and roadside stationary sampling than for fleet average measurements. The fleet average sampling mode captured the effects of traffic conditions on the measured on-road emission ratios, allowing the use of fuel-based emission ratios to assess the validity of traditional "bottom-up" emissions inventories. Using the measured on-road emission ratios, we estimate CO and NOx [NO subscript x] mobile emissions of 175±62 and 10.4±1.3 metric tons/day, respectively, for the gasoline vehicle fleet in Mexicali. Comparisons with similar on-road emissions data from Mexico City indicated that fleet average NO emission ratios were around 20% higher in Mexicali than in Mexico City whereas HCHO and NH3 [NH subscript 3] emission ratios were higher by a factor of 2 in Mexico City than in Mexicali. Acetaldehyde emission ratios did not differ significantly whereas selected aromatics VOCs emissions were similar or smaller in Mexicali. Nitrogen oxides emissions for on-road heavy-duty diesel truck (HDDT) were measured near Austin, Texas, as well as in both Mexican cities, with NOy [NO subscript y] emission ratios in Austin < Mexico City < Mexicali.Mexico. Comisión Ambiental MetropolitanaNational Science Foundation (U.S.) (Grant ATM-0528227)Molina Center for Energy and the EnvironmentUniversity of Texas at AustinLatin American Scholarship Program of American Universitie