Zinc, a metal found in the Earth's crust, is indispensable for human health. In the human body, around 60% of zinc is present in muscles, 30% in bones, and the remaining 10% in skin, hair, pancreas, ...kidneys and plasma. An adequate zinc balance is essential for the maintenance of skeletal growth, development and function. It is also necessary for basic cellular functions including enzyme activation, cell signaling and energy metabolism. Inadequate zinc status is associated with a wide variety of systemic disorders including cardiovascular impairment, musculoskeletal dysfunctions and oromaxillary diseases. In this article, we briefly discuss the role of zinc deficiency in the genesis of various oromaxillary diseases, and explain why adequate zinc homeostasis is vital for the maintenance of oral and general health.
Systemic phosphate homeostasis is tightly controlled by the delicate cross-organ talk among intestine, kidney, bone, and parathyroid glands. The endocrine regulation of phosphate homeostasis is ...primarily mediated by fibroblast growth factor 23 (FGF23), vitamin D, and parathyroid hormone (PTH). Bone-derived FGF23 acts on the proximal tubular epithelial cells of the kidney to partly maintain the homeostatic balance of the phosphate. FGF23, through binding with its cell surface receptors in the presence of klotho, can activate downstream signaling kinases to reduce the functionality of the sodium-phosphate (NaPi) co-transporters of the kidney to influence the systemic phosphate homeostasis. Given the complexity of molecular regulation of phosphate homeostasis, providing information on all aspects of its homeostatic control in a single volume of a book is an overwhelming task. As the Editor, I have organized the chapters that I believe will provide necessary information on the physiologic regulation and pathologic dysregulation of phosphate in health and diseases. Readers will be able to use this volume as a quick reference for updated information on phosphate metabolism without prior acquaintance with the field.
Abstract
We present an incremental version (4FGL-DR3, for Data Release 3) of the fourth Fermi Large Area Telescope (LAT) catalog of
γ
-ray sources. Based on the first 12 years of science data in the ...energy range from 50 MeV to 1 TeV, it contains 6658 sources. The analysis improves on that used for the 4FGL catalog over eight years of data: more sources are fit with curved spectra, we introduce a more robust spectral parameterization for pulsars, and we extend the spectral points to 1 TeV. The spectral parameters, spectral energy distributions, and associations are updated for all sources. Light curves are rebuilt for all sources with 1 yr intervals (not 2 month intervals). Among the 5064 original 4FGL sources, 16 were deleted, 112 are formally below the detection threshold over 12 yr (but are kept in the list), while 74 are newly associated, 10 have an improved association, and seven associations were withdrawn. Pulsars are split explicitly between young and millisecond pulsars. Pulsars and binaries newly detected in LAT sources, as well as more than 100 newly classified blazars, are reported. We add three extended sources and 1607 new point sources, mostly just above the detection threshold, among which eight are considered identified, and 699 have a plausible counterpart at other wavelengths. We discuss the degree-scale residuals to the global sky model and clusters of soft unassociated point sources close to the Galactic plane, which are possibly related to limitations of the interstellar emission model and missing extended sources.
The spatial extension of a γ-ray source is an essential ingredient to determine its spectral properties, as well as its potential multiwavelength counterpart. The capability to spatially resolve ...γ-ray sources is greatly improved by the newly delivered Fermi-Large Area Telescope (LAT) Pass 8 event-level analysis, which provides a greater acceptance and an improved point-spread function, two crucial factors for the detection of extended sources. Here, we present a complete search for extended sources located within 7° from the Galactic plane, using 6 yr of Fermi-LAT data above 10 GeV. We find 46 extended sources and provide their morphological and spectral characteristics. This constitutes the first catalog of hard Fermi-LAT extended sources, named the Fermi Galactic Extended Source Catalog, which allows a thorough study of the properties of the Galactic plane in the sub-TeV domain.
Abstract
Background
Tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) may occasionally show similar cytological and biochemical picture including ADA. In such cases, ...differentiating TPE and MPE is challenging and needs histopathology of pleural tissue which may involve invasive procedures. The present study aims to evaluate the diagnostic accuracy of pleural fluid ADA to serum CRP (ADA/CRP) ratio to discriminate between tuberculous and malignant pleural effusion. In addition, we investigated whether the ratio ADA/CRP adds diagnostic value to ADA.
Methods
This cross-sectional study was conducted in the National Institute of Diseases of the Chest and Hospital (NIDCH), Mohakhali, Dhaka, from July 2021 to February 2022 on diagnosed patients of TPE and malignant pleural effusion MPE. A receiver operating characteristic curve (ROC) was constructed for identifying TPE. The added value of the ADA/CRP ratio to ADA was evaluated using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). A value of
p
< 0.05 was considered statistically significant for all tests.
Results
Fifty-nine patients were enrolled in this study, of which 31 had TPE, and 28 had MPE. Pleural fluid ADA to serum CRP ratio and pleural fluid ADA level was significantly higher in patients with TPE, but there was no significant difference in serum CRP levels between patients with TPE and MPE. At cut off value of > 1.25, pleural fluid ADA to serum CRP ratio had a sensitivity of 93.8%, specificity of 85.2%, and positive and negative predictive values were 88.2% and 92% respectively, in the diagnosis of TPE and area under ROC curve (AUC) was 0.94. The NRI and IDI analyses revealed added diagnostic value of ADA/CRP to ADA.
Conclusion
This study shows that the ADA/CRP ratio improves the diagnostic usefulness of ADA for TPE.
Phosphate is a common ingredient of the daily consumed foods and is absorbed in the intestine and is excreted in the urine through the kidney to maintain the homeostatic balance. For adults, the ...Recommended Dietary Allowance (RDA) for phosphorus is around 700 mg/day. The change in dietary habits resulted in far more phosphate consumption (almost double) than the RDA, contributing to increased cardiovascular diseases, kidney diseases, and tumor formation. Due to a lack of clinical appreciation for the long‐term consequences of chronic phosphate burden on non‐communicable disorders, it is rapidly becoming a global health concern. The possible association between dysregulated phosphate metabolism and obesity is not studied in‐depth, mainly because such an association is believed to be nonexistent. However, in the animal model of obesity, serum phosphate level was higher than their non‐obese controls. In a similar observation line, significantly higher salivary phosphate levels were detected in obese children compared to normal‐weight children. Of clinical importance, despite the significant increase of salivary phosphate levels in obese children, the plasma phosphate levels did not change in samples collected from the same group of children. Such disparity between plasma and saliva raised the possibility that human salivary phosphate levels may be an early biomarker of childhood obesity.
Inorganic phosphate (Pi) is an essential nutrient for human health. Due to the changes in our dietary pattern, dietary Pi overload engenders systemic phosphotoxicity, including excessive Pi‐related ...vascular calcification and chronic tissue injury. The molecular mechanisms of the seemingly distinct phenotypes remain elusive. In this study, we investigated Pi‐mediated cellular response in HEK293 and HeLa cells. We found that abnormally high Pi directly mediates diverse cellular toxicity in a dose‐dependent manner. Up to 10 mM extracellular Pi promotes cell proliferation by activating AKT signaling cascades and augmenting cell cycle progression. By introducing additional Pi, higher than the concentration of 40 mM, we observed significant cell damage caused by the interwoven Pi‐related biological processes. Elevated Pi activates mitogen‐activated protein kinase (MAPK) signaling, encompassing extracellular signal‐regulated kinase 1/2 (ERK1/2), p38 and Jun amino‐terminal kinase (JNK), which consequently potentiates Pi triggered lethal epithelial‐mesenchymal transition (EMT). Synergistically, high Pi‐caused endoplasmic reticulum (ER) stress also contributes to apparent apoptosis. To counteract, Pi‐activated AKT signaling promotes cell survival by activating the mammalian target of rapamycin (mTOR) signaling and blocking ER stress. Pharmacologically or genetically abrogating Pi transport, the impact of high Pi‐induced cytotoxicity could be reduced. Taken together, abnormally high extracellular Pi results in a broad spectrum of toxicity by rewiring complicated signaling networks that control cell growth, cell death, and homeostasis.
Abstract
The Large Area Telescope (LAT), the primary instrument for the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering ...the energy range from 30 MeV to more than 300 GeV. We describe the performance of the instrument at the 10 yr milestone. LAT performance remains well within the specifications defined during the planning phase, validating the design choices and supporting the compelling case to extend the duration of the Fermi mission. The details provided here will be useful when designing the next generation of high-energy gamma-ray observatories.
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