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Radiology May 2022Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on... (Observational Study)
Observational Study
Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on serial chest CT scans in COVID-19 survivors discharged from hospital at up to 1-year follow-up. Materials and Methods Adult patients with COVID-19 discharged between March 2020 and June 2020 were prospectively evaluated at 3 months and 1 year through systematic assessment of symptoms, functional impairment, and thoracic CT scans as part of the PHENOTYPE study, an observational cohort study in COVID-19 survivors. Lung function testing was limited to participants with CT abnormalities and/or persistent breathlessness. Bonferroni correction was used. Results Eighty participants (mean age, 59 years ± 13 [SD]; 53 men) were assessed. At outpatient review, persistent breathlessness was reported in 37 of the 80 participants (46%) and cough was reported in 17 (21%). CT scans in 73 participants after discharge (median, 105 days; IQR, 95-141 days) revealed persistent abnormalities in 41 participants (56%), with ground-glass opacification (35 of 73 participants [48%]) and bands (27 of 73 participants [37%]) predominating. Unequivocal signs indicative of established fibrosis (ie, volume loss and/or traction bronchiectasis) were present in nine of 73 participants (12%). Higher admission serum C-reactive protein (in milligrams per liter), fibrinogen (in grams per deciliter), urea (millimoles per liter), and creatinine (micromoles per liter) levels; longer hospital stay (in days); older age (in years); and requirement for invasive ventilation were associated with CT abnormalities at 3-month follow-up. Thirty-two of 41 participants (78%) with abnormal findings at 3-month follow-up CT underwent repeat imaging at a median of 364 days (range, 360-366 days), with 26 (81%) showing further radiologic improvement (median, 18%; IQR, 10%-40%). Conclusion CT abnormalities were common at 3 months after COVID-19 but with signs of fibrosis in a minority. More severe acute disease was linked with CT abnormalities at 3 months. However, radiologic improvement was seen in the majority at 1-year follow-up. ClinicalTrials.gov identifier: NCT04459351. © RSNA, 2022
Topics: COVID-19; Dyspnea; Fibrosis; Hospitals; Humans; Lung; Patient Discharge; Tomography, X-Ray Computed
PubMed: 34609195
DOI: 10.1148/radiol.2021211746 -
JAMA Pediatrics Oct 2019The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear.
IMPORTANCE
The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear.
OBJECTIVE
To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019.
EXPOSURES
Maternal urinary fluoride (MUFSG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women.
MAIN OUTCOMES AND MEASURES
Children's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score.
RESULTS
Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUFSG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUFSG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUFSG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUFSG was associated with a 4.49-point lower IQ score (95% CI, -8.38 to -0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, -2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, -7.16 to -0.14) in boys and girls.
CONCLUSIONS AND RELEVANCE
In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.
PubMed: 31424532
DOI: 10.1001/jamapediatrics.2019.1729 -
Medicine Sep 2022Anaphylactic shock is the severe state of the allergic reaction, which is rapid in onset and fatal. This is the first study that discusses the anaphylactic shock of...
BACKGROUND
Anaphylactic shock is the severe state of the allergic reaction, which is rapid in onset and fatal. This is the first study that discusses the anaphylactic shock of exenatide reexposure in the patient who has interrupted exenatide treatment.
PATIENT CONCERNS
A 47-year-old man was treated with exenatide owing to high blood glucose and obesity. Then he developed localized urticarial on the face, white lip, hands tremble, nausea, vomit, chest stuffiness, dizziness, accompanying with confusion and dyspnea. His blood glucose was 4.6 millimole per liter (mmol/L) and blood pressure was 85/50 millimeters of mercury (mm Hg).
DIAGNOSIS
Exenatide-induced anaphylactic shock was considered.
INTERVENTIONS
The emergency electrocardiogram was performed. The patient was treated with dexamethasone sodium phosphate and calcium gluconate, combined with exenatide withdrawal. He also received oral antiallergic agents and intravenous nutrition treatment.
OUTCOMES
After antishock treatment, the clinical response gradually alleviated.
LESSONS
Although exenatide is not prone to anaphylaxis, it is the synthetic peptide that can induce antibody formation. Exenatide has immunogenicity with the potential to elicit an allergic reaction upon administration. Clinicians should always pay more attention to the anaphylactic shock of exenatide, when prescribing for diabetics.
Topics: Anaphylaxis; Anti-Allergic Agents; Blood Glucose; Calcium Gluconate; Exenatide; Humans; Male; Mercury; Middle Aged
PubMed: 36181058
DOI: 10.1097/MD.0000000000030805 -
Science (New York, N.Y.) Apr 2018Major changes in atmospheric and ocean chemistry occurred in the Paleoproterozoic era (2.5 to 1.6 billion years ago). Increasing oxidation dramatically changed Earth's...
Major changes in atmospheric and ocean chemistry occurred in the Paleoproterozoic era (2.5 to 1.6 billion years ago). Increasing oxidation dramatically changed Earth's surface, but few quantitative constraints exist on this important transition. This study describes the sedimentology, mineralogy, and geochemistry of a 2-billion-year-old, ~800-meter-thick evaporite succession from the Onega Basin in Russian Karelia. The deposit consists of a basal unit dominated by halite (~100 meters) followed by units dominated by anhydrite-magnesite (~500 meters) and dolomite-magnesite (~200 meters). The evaporite minerals robustly constrain marine sulfate concentrations to at least 10 millimoles per kilogram of water, representing an oxidant reservoir equivalent to more than 20% of the modern ocean-atmosphere oxidizing capacity. These results show that substantial amounts of surface oxidant accumulated during this critical transition in Earth's oxygenation.
PubMed: 29567810
DOI: 10.1126/science.aar2687 -
Nano Convergence May 2022Reactive oxygen species (ROS) regulate various physiological and pathological conditions in cells by interacting with signaling molecules and inducing oxidative stress....
Reactive oxygen species (ROS) regulate various physiological and pathological conditions in cells by interacting with signaling molecules and inducing oxidative stress. Therefore, sensitive monitoring of ROS levels in living cells is important to track cellular state and study the complex role of ROS in the development of various pathologies. Herein, we present an optically tunable plasmonic interface covered with graphene to monitor cellular ROS levels with superior sensitivity and cellular comfortability. As a sensing principle, we employed plasmon resonance energy transfer (PRET)-based spectral quenching dips modulated by redox-active cytochrome c for real-time monitoring. By transferring graphene layers to plasmonic nanoparticles immobilized on a glass substrate, the scattering profiles of the nanoprobes were adjusted in terms of the position, width, and intensity of the peaks to determine the optimal conditions for measuring the PRET signal. Using the optimized graphene-covered plasmonic nanoprobe, we obtained calibration curves over a wide concentration range from femtomoles to millimoles for hydrogen peroxide based on the change in the PRET signal. Before monitoring cellular ROS, we confirmed that a high density of cells adhered well to the graphene-covered plasmonic interface by observing immunofluorescence images of the cytoskeleton of the immobilized cells. Finally, we monitored the real-time ROS generated by the cells under oxidative stress conditions by directly measuring the spectral changes of the probes around the cells. We believe that the proposed graphene-covered tunable plasmonic interface has versatile applicability for investigating cellular stress and disease progression by monitoring ROS levels under various cellular conditions.
PubMed: 35604511
DOI: 10.1186/s40580-022-00315-9 -
ACS Chemical Biology Aug 2008A general method for isotopic labeling of the purine base moiety of nucleotides and RNA has been developed through biochemical pathway engineering in vitro. A synthetic...
A general method for isotopic labeling of the purine base moiety of nucleotides and RNA has been developed through biochemical pathway engineering in vitro. A synthetic scheme was designed and implemented utilizing recombinant enzymes from the pentose phosphate and de novo purine synthesis pathways, with regeneration of folate, aspartate, glutamine, ATP, and NADPH cofactors, in a single-pot reaction. Syntheses proceeded quickly and efficiently in comparison to chemical methods with isolated yields up to 66% for 13C-, 15N-enriched ATP and GTP. The scheme is robust and flexible, requiring only serine, NH4+, glucose, and CO2 as stoichiometric precursors in labeled form. Using this approach, U-13C- GTP, U-13C, 15N- GTP, 13C 2,8- ATP, and U-15N- GTP were synthesized on a millimole scale, and the utility of the isotope labeling is illustrated in NMR spectra of HIV-2 transactivation region RNA containing 13C 2,8-adenosine and 15N 1,3,7,9,2-guanosine. Pathway engineering in vitro permits complex synthetic cascades to be effected, expanding the applicability of enzymatic synthesis.
Topics: Adenosine Triphosphate; Carbon Isotopes; Chromatography, High Pressure Liquid; Cloning, Molecular; Enzymes; Escherichia coli; Guanosine Triphosphate; Molecular Structure; Nitrogen Isotopes; Plasmids; Protein Engineering; Purine Nucleotides; RNA; Substrate Specificity
PubMed: 18707057
DOI: 10.1021/cb800066p -
The Journal of Clinical Investigation May 1974The present studies were performed to determine whether dipeptide absorption in human jejunum exhibits the characteristics of carrier-mediated transport. 15-cm jejunal...
The present studies were performed to determine whether dipeptide absorption in human jejunum exhibits the characteristics of carrier-mediated transport. 15-cm jejunal segments from human volunteers were perfused with test solutions containing varying amounts of either glycylglycine, glycylleucine, glycine, leucine, glycylglycine with leucine or glycine, glycylglycine with glycylleucine, or glycylleucine with an equimolar mixture of free glycine and leucine. Jejunal absorption rates of both glycylglycine and glycylleucine followed the kinetics of a saturable process. The K(m) value in millimoles/liter of glycylglycine was significantly greater than the K(m) value of glycylleucine (43.3+/-2.6 vs. 26.8+/-5.9, P < 0.05); and the K(m) value of glycine was also significantly greater than the K(m) value of leucine (42.7+/-7.5 vs. 20.4+/-5.4, P < 0.05). While overlapping occurred among the K(m) values of free amino acids and dipeptides, the transport kinetics of dipeptides were characterized by higher V(max) values (in micromoles per minute per 15 centimeters) than those of free amino acids. For example, the V(max) values for glycylglycine and glycine were 837+/-62 and 590+/-56, respectively (P < 0.02). While jejunal absorption rates of glycylglycine were not significantly affected by free leucine or free glycine, they were competitively inhibited by glycylleucine. The jejunal absorption rate of glycylleucine was not significantly altered by an equimolar mixture of free glycine and leucine. The selective absorption of dipeptides was investigated by infusing three equimolar mixtures, each containing two different dipeptides. Among the three dipeptides examined, glycylglycine was the least absorbed. There was no significant difference between the absorption of glycylleucine and leucylglycine. The above studies suggest that absorption of both glycylglycine and glycylleucine is mediated by a carrier which is not shared with free neutral amino acids; and that both COOH- and NH(2)-terminal amino acids appear to be influential in imposing the affinity of a dipeptide for the absorption sites.
Topics: Biological Transport; Dipeptides; Glycine; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Jejunum; Kinetics; Leucine; Male
PubMed: 4825229
DOI: 10.1172/JCI107685 -
Journal of Dairy Science Jun 2018Free radicals are reactive and unstable waste molecules produced by cells, responsible of damages and alteration on DNA, proteins, and fat. The daily intake of... (Comparative Study)
Comparative Study
Free radicals are reactive and unstable waste molecules produced by cells, responsible of damages and alteration on DNA, proteins, and fat. The daily intake of antioxidant compounds, acting against free radicals and their detrimental effects, is essential for human health. Milk contains several compounds with antioxidant activity, and the sum of their reducing potential blocking free radicals development is defined as total antioxidant activity (TAA). This novel trait has been described in literature both in individual and bulk cow milk, but there are no reports from other dairy species. Therefore, the present study aimed to investigate phenotypic variation of TAA in individual samples of buffalo (n = 105), goat (n = 112), and sheep (n = 198) milk. Total antioxidant activity was measured through a reference spectrophotometric method, and expressed as millimoles per liter of Trolox equivalents (TE). The greatest TAA was observed in sheep milk, averaging 7.78 mmol/L of TE and showing also the broadest phenotypic variation expressed as coefficient of variation (13.98%). Significantly lower TAA values were observed for buffalo (7.35 mmol/L of TE) and goat (6.80 mmol/L of TE) milk, with coefficients of variation of 8.18 and 8.47%, respectively. Total antioxidant activity exhibited weak correlations with milk yield and chemical composition. Phenotypic values of TAA presented in this study will be used to assess the ability of mid-infrared spectroscopy to predict this new trait and thus to collect data at the population level.
Topics: Animals; Antioxidants; Buffaloes; Cattle; Female; Goats; Milk; Sheep; Spectrophotometry; Spectrophotometry, Infrared
PubMed: 29550119
DOI: 10.3168/jds.2017-13792 -
Cureus Jun 2018Thyrotoxic periodic paralysis (TPP) and cardiomyopathy are two established complications of thyrotoxicosis. Emergent management is essential as TPP and cardiac events...
Thyrotoxic periodic paralysis (TPP) and cardiomyopathy are two established complications of thyrotoxicosis. Emergent management is essential as TPP and cardiac events secondary to thyrotoxic cardiomyopathy can be fatal. We report a unique case of a patient with Graves' disease presenting with symptoms secondary to both these complications. A 34-year-old Hispanic male, diagnosed with Graves' disease, non-compliant with his medications, presented to the emergency room (ER) with complaints of generalized weakness, palpitations, chest pain and multiple episodes of nausea and vomiting for one day. On presentation, the patient was tachycardiac, had a systolic flow murmur and decreased motor strength in all extremities. Blood work showed a potassium of 1.8 millimoles per liter, cardiac troponin of 0.04 nanograms per milliliter and a thyroid panel consistent with hyperthyroidism. Electrocardiogram showed atrial flutter. In the ER, Propranolol, Propylthiouracil and Hydrocortisone were administered to prevent thyroid storm. Potassium was repleted, and the patient developed rebound hyperkalemia. He was given calcium gluconate, insulin, sodium polystyrene and admitted to the medical intensive care unit (MICU) for further management. Echocardiogram revealed severely decreased left ventricular systolic function and an ejection fraction of 26-30%. He was diagnosed with cardiomyopathy secondary to thyrotoxicosis. He was stabilized with Methimazole, Propranolol, Lisinopril and discharged on day nine with these medications and an outpatient follow-up appointment. Thyrotoxicosis can be life-threatening. This case shows a unique instance where a Hispanic patient presented with two complications of this phenomena. The pathogenesis of TPP involves increased responsiveness of the beta-adrenergic receptors, which leads to increased activity of the Sodium/Potassium (Na/K) ATPase pump and a transcellular shift of potassium into cells. The condition can resolve acutely with the administration of potassium. It is important to monitor the rate of potassium replacement as rebound hyperkalemia can occur, as this case demonstrates. Propranolol is an integral part of treatment as it is a beta-adrenergic receptor blocker and blocks the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) in high doses. Thyrotoxic cardiomyopathy is one of the many cardiac complications that can be precipitated by Graves' disease. One probable cause is the chronic tachycardia that patients with hyperthyroidism develop. Treatment entails managing the hyperthyroidism by starting the patient on beta blockers and anti-thyroid drugs or radioactive iodine uptake. Diuretics can be started to manage patients with heart failure. It is important to identify and treat the condition immediately to prevent grave complications.
PubMed: 30131930
DOI: 10.7759/cureus.2837 -
ChemSusChem Feb 2024The first enantioselective reduction of 2-substituted cyclic imines to the corresponding amines (pyrrolidines, piperidines, and azepines) by imine reductases (IREDs) in...
The first enantioselective reduction of 2-substituted cyclic imines to the corresponding amines (pyrrolidines, piperidines, and azepines) by imine reductases (IREDs) in non-conventional solvents is reported. The best results were obtained in a glycerol/phosphate buffer 1 : 1 mixture, in which heterocyclic amines were produced with full conversions (>99 %), moderate to good yields (22-84 %) and excellent S-enantioselectivities (up to >99 % ee). Remarkably, the process can be performed at a 100 mM substrate loading, which, for the model compound, means a concentration of 14.5 g L . A fed-batch protocol was also developed for a convenient scale-up transformation, and one millimole of substrate 1 a was readily converted into 120 mg of enantiopure amine (S)-2 a with a remarkable 80 % overall yield. This aspect strongly contributes to making the process potentially attractive for large-scale applications in terms of economic and environmental sustainability for a good number of substrates used to produce enantiopure cyclic amines of high pharmaceutical interest.
Topics: Oxidoreductases; Imines; Solvents; Stereoisomerism; Amines
PubMed: 37751248
DOI: 10.1002/cssc.202301243