Oral Manifestations in Patients with COVID-19: A 6-Month Update.

This is the first update of the previously published living systematic review that summarized evidence on the prevalence of oral signs and symptoms in patients with COVID-19. Hitherto, 183 studies were included, reporting data from 64,876 patients with COVID-19 worldwide. The overall prevalence of taste disorders was 38% (95% CI = 22% to 56%, I2 = 98%). Hypogeusia, dysgeusia, and ageusia were also evaluated by a meta-analysis, and the pooled prevalence was 34% for hypogeusia, 33% for dysgeusia, and 26% for ageusia. Taste disorders were associated with a positive COVID-19 test (odds ratio [OR] = 7.54, 95% CI = 5.24 to 10.86, I2 = 93%, P < 0.00001), showing high certainty of evidence. However, the association between taste disorders and mild/moderate severity of COVID-19 (OR = 1.63, 95% CI = 1.33 to 1.99, I2 = 69%, P < 0.0001) and female patients with COVID-19 (OR = 1.77, 95% CI = 1.26 to 2.48, I2 = 79%, P = 0.001) presented low certainty of evidence. Xerostomia was a new feature of this update, and the pooled data demonstrated a prevalence of 43% (95% CI = 36% to 50%, I2 = 71%) in patients with COVID-19. Regarding oral mucosal lesions, the most common clinical pattern was aphthous like, followed by herpes-like lesions, candidiasis, glossitis/depapillation/geographic tongue, parotitis, and angular cheilitis. Oral lesions were more frequent in the tongue, lips, and palate, presenting miscellaneous clinical aspects that are more likely to represent coinfections. Therefore, the reanalysis of current evidence suggests the triad xerostomia, taste dysfunction, and oral mucosal lesions as common manifestations in patients with COVID-19. However, these outcomes are under discussion, and more studies will be necessary to confirm their association with direct SARS-CoV-2 infection in the oral cavity.

Standardization of 223Ra by live-time anticoincidence counting and gamma-ray emission determination.

From a commercial supplier, three independent lots of an aqueous solution containing 223Ra in equilibrium with its deteriorating progeny were considered for standardization, by using live-time anticoincidence counting (LTAC) in the Laboratório Nacional de Metrologia das Radiações Ionizantes (LNMRI) Brazil. The ionization chamber calibration factors were obtained using measurements of independent lots of 223Ra in LTAC considering the absolute method in order to evaluate the constancy and reproducibility of the standardization. The calibration factors of three high-performance well-type ionization chamber systems and four commercial well-type ionization chambers were determined. The LTAC results showed that lots 2 and 3 were 1069.88 and 1097.44 kBq/kg, with corresponding relative standard uncertainties 0.12% and 0.20%, respectively. The spectrometry method results of each lot value were classified as positive by ANOVA hypothesis testing. The emission probabilities relating to the X- and γ-rays in region from 81 to 830 keV ware determined. Hence, LNMRI can provide calibration services for 223Ra.

Oral Manifestations in Patients with COVID-19: A Living Systematic Review.

This living systematic review aims to summarize evidence on the prevalence of oral signs and symptoms in patients with COVID-19. The review was reported per the PRISMA checklist, and the literature search was conducted in 6 databases and in gray literature. Studies published in any language mentioning oral symptoms and signs in patients with COVID-19 were included. The risk of bias was assessed by the Joanna Briggs Institute appraisal tools. The certainty of evidence was evaluated through GRADE assessment. After a 2-step selection, 40 studies were included: 33 cross-sectional and 7 case reports. Overall, 10,228 patients (4,288 males, 5,770 females, and 170 unknown) from 19 countries were assessed. Gustatory impairment was the most common oral manifestation, with a prevalence of 45% (95% CI, 34% to 55%; I2 = 99%). The pooled eligible data for different taste disorders were 38% for dysgeusia and 35% for hypogeusia, while ageusia had a prevalence of 24%. Taste disorders were associated with COVID-19 (odds ratio [OR], 12.68; 95% CI, 6.41 to 25.10; I2 = 63%; P < 0.00001), mild/moderate severity (OR, 2.09; 95% CI, 1.25 to 3.49; I2 = 66%; P = 0.005), and female patients (OR, 1.64; 95% CI, 1.23 to 2.17; I2 = 70%; P = 0.0007). Oral mucosal lesions presented multiple clinical aspects, including white and erythematous plaques, irregular ulcers, small blisters, petechiae, and desquamative gingivitis. Tongue, palate, lips, gingiva, and buccal mucosa were affected. In mild cases, oral mucosal lesions developed before or at the same time as the initial respiratory symptoms; however, in those who required medication and hospitalization, the lesions developed approximately 7 to 24 d after onset symptoms. Therefore, taste disorders may be common symptoms in patients with COVID-19 and should be considered in the scope of the disease's onset and progression. Oral mucosal lesions are more likely to present as coinfections and secondary manifestations with multiple clinical aspects (PROSPERO CRD42020184468).

Measurement of the absolute gamma emission intensities from the decay of Th-229 in equilibrium with progeny.

There are few long-lived radionuclides yielding high intensity gamma-rays emission with energies ranging from 100 keV to 500 keV that can be applied as radioactive gamma standard to calibrate HPGe detectors. Furthermore, this energy range represents the main emitted energies of the majority of radionuclides used in nuclear medicine. The Brazilian National Laboratory for Ionizing Radiation Metrology (LNMRI/IRD/CNEN) has attempted to identify radionuclides that have the potential to be used as a calibration source due to their long half-life as well as their emission spectrum. Hence, LNMRI promotes standardization studies of gamma-emitting radionuclides that meet these criteria on order to disseminate them. Thorium-229, with its well-defined energies and relatively high intensities, is one such candidate radionuclide for the energy and full-energy peak efficiency calibration of high-purity gamma spectrometers. Thorium-229 was standardized by the method of 4παß(LS)-γ(NaI(Tl)) live timed anticoincidence counting. The emission intensities of gamma-rays associated with the decay of 229Th have been determined by HPGe gamma ray spectrometry with accuracy and precision. The results are in agreement with current literature data.

Rapid and accurate assessment of the activity measurements in Brazilian hospitals and clinics.

Traceability in Nuclear Medicine Service (NMS) measurements was checked by the Institute of Radioprotection and Dosimetry (IRD) through the Institute of Energy and Nuclear Research (IPEN). In 2016, IRD ran an intercomparison program and invited Brazilian NMS authorized to administer 131I to patients. Sources of 131I were distributed to 33 NMSs. Three other sources from the same solution were sent to IRD, after measurement at IPEN. These sources were calibrated in the IRD reference system. A correction factor of 1.013 was obtained. Ninety percent of the NMS comparisons results are within ±10% of the National Laboratory of Metrology of Ionizing Radiation (LNMRI) value, the Brazilian legal requirement.

134Cs activity standardization by 4πß(LS)-γ(NaI-Tl) anticoincidence counting and submission to international reference system.

From a commercial supplier a solution containing 134Cs has been standardized at National Laboratory for Ionizing Radiation Metrology (LNMRI) for the first time using three Liquid scintillation based measurement. These measurement methods are 4πß-γ live-timed anticoincidence counting, 4πß-γ coincidence counting and 3H-standard efficiency tracing with the CNET methods. The results obtained by anticoincidence counting was adopted as reference value and its combined uncertainty was 0.38%. The agreement of this reference value with coincidence counting and CNET methods were 0.39% and 0.34% respectively and were in consistency with each uncertainty method. The weighted mean results coincidence counting and CNET methods are also in close agreement 0.03% with anticoincidence counting method and meets the requirement of primary and national standard. This standardization was made in order to reduce the uncertainty in 134Cs measurement in Brazil and also following a request made by Bureau International des Poids and Mesures for new submission to International Reference System. The LNMRI last submission was made in 1987. Therefore from a 134Cs master solution a NIST ampoules was prepared and LNMRI/IRD submitted it to the International Reference System, Bureau International of Poids and Measures (SIR/BIPM). In this paper will be analyzed the LNMRI measurement and performance each measurement methods and also take into account the reference value of KCDB, we determined also the 134Cs gamma emission probabilities of main energy.

Determination of impurities in (124)I samples by high resolution gamma spectrometry.

(124)I is a radionuclide used in the diagnosis of tumors. The National Health Agency requires identification and activity measurement of impurities. Using gamma spectrometry with an efficiency calibrated high-purity germanium detector, impurities (125)I and (126)I in an (1)(24)I production sample were identified. Activity ratios of (125)I and (126)I to (124)I were approximately 0.5% and 98%, respectively.

Radioactivity measurements of 177Lu, 111In and 123I by different absolute methods.

The activities of (177)Lu, (111)In and (123)I solutions have been absolutely determined using three different measurement methods. (177)Lu solution was standardized using the 4πß(PC)-γ(NaI) coincidence and 4πß(LS)-γ(NaI) live-timed anticoincidence methods. For the (111)In and (123)I solutions, besides these two mentioned methods, the coincidence sum-peak method was also applied. The measured activities results using these different methods are consistent within the evaluated experimental uncertainties demonstrating the equivalence of these methods. As an additional contribution to nuclear data, the half-lives have been determined using a well type IG12 ionization chamber.

Standardization of 65Zn by sum-peak method.

A commercial solution of (65)Zn was standardized by the sum peak-method using a planar HPGe detector. The activity results were compared with measurements made with a well type 4πγ ionization chamber, which is traceable to BIPM.RI (II)-K2.Zn-65 key-comparison performed in 2002. The sum-peak value was 42.79 kBq/g and the ionization chamber value was 42.74 kBq/g both at the reference date. The uncertainty obtained in the sum peak standardization was 0.25% (k=1), and in the ionization chamber was 0.85% (k=1). The results showed that sum-peak method can be used in (65)Zn standardization and this method is easier, simpler and more practical than others methods.

Standardization of (166m)Ho and 243Am/239Np by live-timed anti-coincidence counting with extending dead time.

The National Laboratory for Metrology of Ionizing Radiation (LNMRI)/Brazil acquired (166m)Ho and (243)Am/(239)Np solutions from commercial suppliers in order to realize primary standardization and therefore reducing the associated uncertainties. The method used in the standardization was the live-timed 4πß(LS)-γ(ΝaI(Tl)) anticoincidence counting. The live-timed anticoincidence system is operated since 2006 in LNMRI and is composed of two MTR2 modules donated by Laboratoire National Henri Becquerel (LNE-LNHB)/France. The data acquisition system uses a homemade LabView program and an Excel file for calculus. These systems have been used for primary standardization at LNMRI for many radionuclides and recently took part in the (124)Sb and (177)Lu International Key Comparisons with good performance.

Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection.

Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3-53 years, median 24) with aplastic anemia to reduce graft rejection. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine-methotrexate. The number of prior transfusions was 0-276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10 secondary rejection at 28-1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (>/=50 U) it was 43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was 56%; patients who received 15 transfusions was 78 and 50%, respectively (P=0.01), whereas it was 67 and 28% for 50 transfusions, respectively (P=0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to <50 transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients.

Low frequency oscillations in semi-insulating GaAs: a nonlinear analysis.

We have observed low frequency current oscillations in a semi-insulating GaAs sample grown by low temperature molecular beam epitaxy. For this, an experimental setup proper to measure high impedance samples with small external noise was developed. Spontaneous oscillations in the current were observed for some bias conditions. Although measurements were carried out from room temperature down to liquid helium, the dynamical analysis was carried out around 200 K where the signal to noise ratio was fairly favorable. To increase the data quality we have also used a noise reduction algorithm suitably developed for nonlinear systems. We observed attractors having low embedding dimension, limit cycle bifurcations, and chaotic behavior characteristic of nonlinear dynamical processes in route to chaos. Attractor reconstruction, Poincare sections, Lyapunov exponents, and correlation dimension were also analyzed.

Comparative bioavailability of two oral L-thyroxine formulations after multiple dose administration in patients with hypothyroidism and its relation with therapeutic endpoints and dissolution profiles.

The aim of the present study was to evaluate the bioequivalence and therapeutic equivalence of the two most commonly prescribed L-thyroxine (monsodium L-thyroxine hydrate, CAS 25416-65-3) formulations in Brazil in patients treated for hypothyroidism. Twenty-four patients received 100 micrograms L-thyroxine daily of either Puran T4 (test) or the Brazilian reference formulation (reference) during 42 days, in a two-period crossover design. Serum samples obtained over a 24-h interval were analyzed for their total T4 concentration by a chemiluminescent immunoassay. Content and uniformity of the tablets and dissolution studies were also assessed according to USP 24 monograph using an isocratic HPLC-UV system and a rotating-paddle method. The mean pharmacokinetic parameters for total T4, expressed as geometric means (CV), for the test and reference were, respectively: Cmax (microgram/dl) 9.8 (14.3%) and 10.8 (14.9%); AUC0-24 h (microgram/dl.h) 206.8 (13.9%) and 230.4 (14.9%). Median values (90% CI) for Tmax (h) were 3 (2-3) and 2 (2-4) for the test and reference, respectively. 90% CI for ratios of LogCmax and LogAUC0-24 h were 86.6-94.9 and 86.3-93.4, respectively. Although the test exhibited values of Cmax and AUC0-24 h around 10% lower than the reference, these formulations must be considered bioequivalent since the 90% CI for both Cmax and AUC0-24 h mean ratio were within the 80-125% interval as proposed by the US Food and Drug Administration and the Brazilian legislation. TSH dosages within the normal range further support therapeutic equivalence between the two formulations. Dissolution data were roughly in agreement with in vivo results since both formulations comply with the USP dissolution criteria although the test tablets had a slower dissolution rate than the reference tablets. As a conclusion, the two oral formulations of L-thyroxine are both bioequivalent and therapeutically equivalent although presenting a small difference in their extent of absorption. Noteworthy, the dissolution profiles of the tablets correlate well with their bioavailability in the present experimental conditions.