Internal dose rate due to intake of uranium and thorium by fish from a dam reservoir associated with a uranium mine in Brazil.

Uranium mining can cause environmental impacts on non-human biota around mine sites. Because of this, the reduction in non-human biota exposure becomes an important issue. Environmental radioprotection results from the evolution of human radioprotection; it is based on dose rate to non-human biota and uses, as a biological target, and has harmful effects on populations. In the present study, a flooded impoundment created following dam construction in a uranium mine plant undergoing decommissioning was investigated. Internal dose rates due to activity concentration of natural uranium (Unat) and 232Th in omnivorous, phytophagous, and carnivorous fish species were estimated. Radionuclide activity concentrations were obtained by spectrophotometry with arsenazo III in the visible range. The dose rate contribution of 232Th was lower than that of Unat. There were no differences between the internal dose rates to studied fish species due to 232Th, but there were differences for Unat. A dose rate of 2.30·10-2 µGy∙d-1 was found due to the two studied radionuclides. Although this value falls below the benchmark for harmful effects, it is important to acknowledge that the assessment did not account for other critical radionuclides from uranium mining, which also contribute to the internal dose. Moreover, the study did not assess external doses. As a result, the possibility cannot be excluded that dose rates at the study area overcome the established benchmarks for harmful effects.

Application of radiological assessment as water quality criterion for effluent release in a Brazilian uranium mine.

Uranium mining causes several radiological impacts on the surrounding environment, notably in the water bodies, mainly due to the release of long half-life radionuclides from the 238U and 232Th series. The Ore Treatment Unit, an old uranium mine undergoing decommissioning, has three points of liquid effluent release (#014, #025, and #076). For current study, 78 samples of water were collected at #014, 33 samples at #025, and 63 samples at #076. The radionuclides were analyzed by gross alpha count, gross beta count, and by arsenazo spectrophotometry. Analyses were carried out using the radiological water quality criterion established by World Health Organization and other organizations, together with the Brazilian legislation, to assess if the released effluents may be used unrestrictedly by the individuals of the public. At #014, the mean values of activity concentration (AC), in Bq·L-1, were as follows: Unat = 0.107, 226Ra = 0.035, 210Pb = 0.031, 232Th = 0.007, and 228Ra = 0.049. At #025 the mean values of AC, in Bq·L-1, were as follows: Unat = 0.086, 226Ra = 0.015, 210Pb = 0.028, 232Th = 0.006, and 228Ra = 0.032. Finally, at point #076, the mean AC values, in Bq·L-1, were as follows: Unat = 3.624, 226Ra = 0.074, 210Pb = 0.054, 232Th = 0.013, and 228Ra = 0.069. The current study showed that natural radionuclides were not in secular equilibrium. Despite uranium presented its values outside the limits of guidance levels, it can be state that the unrestricted use of effluents released in the three water bodies is authorized from the radiological point of view. In terms of dose rate, the releases at three points were within the radiological limits of potability. On the other hand, in an additional analysis, #76 presented chemical toxicity above the authorized value, pointing the need of restricted use of water from the point of view of chemical toxicity.

Excess lifetime cancer risk due to ingestion of fish from a dam reservoir associated with a nuclear facility in Brazil.

Fish from a Funil dam reservoir associated with a Nuclear Fuel Factory were sampled aiming to assess the radiological risk due to ingestion. Funil dam reservoir is a strategic site, once it receives effluent from the industrial complex that performs isotopic enrichment of uranium and conversion of UF6. The mean activity concentrations obtained for 40K, 226Ra, 228Ra and 228Th were 57.81, 0.41, 0.92 and 0.49 Bq·kg-1, respectively. Lifetime cancer risk was estimated in ∼10-5 and no action needs to be taken.

Exercise and bariatric surgery: A systematic review and meta-analysis of the feasibility and acceptability of exercise and controlled trial methods.

This systematic review and meta-analysis assessed the feasibility and acceptability of exercise and controlled trial methods in adults awaiting or having undergone bariatric surgery (BS). Search methods used to identify relevant articles were inclusion of articles identified in a systematic review, new database search of articles published 2019-2021, and hand searching reference lists. Titles/abstracts and full-texts were screened by two reviewers independently against inclusion criteria: adults awaiting or having undergone BS, controlled trial, exercise group compared with a comparison group without exercise. Twenty-eight articles were reviewed; most interventions were supervised, performed after BS, and lasted ≤13 weeks. Pooled data for exercise intervention attendance and dropout rates were 84% (k = 10) and 5% (k = 19), respectively, though possibly misestimated due to poor/selective reporting. Median study and recruitment duration were 18 weeks and 24 months, respectively, with a pooled enrollment rate of 2.5 participants/month. Pooled data for refusal to participate, enrollment, and retention rates were 23% (k = 16), 43% (k = 18), and 87% (k = 26), respectively. Despite the lack of data available in studies included, exercise and controlled trial methods seem feasible and acceptable for adults awaiting or having undergone BS. To better identify methodological or practical challenges, and assess bias, better reporting of feasibility and acceptability indicators is needed in future studies.

Assessment of released natural radionuclides by waste rock pile and mining pit associated with a uranium mine at Caldas, Minas Gerais, Brazil.

The Ore Treatment Unit was a uranium mining company that is currently being decommissioned. The local rainfall index makes it necessary to release effluents into the environment. After releasing, the wastewater is available for unrestricted use. Current study aims to use national and international recommendations to assess the radiological potability of released effluents at one of the three points of company's interface with the environment. Twenty-four samples of water were collected and activity concentrations (AC) were obtained by gross alpha count, gross beta count, and for arsenazo spectrophotometry. Statistical analysis techniques were applied to the data with the purpose of understanding the results for the soluble, particulate, and total fractions. The mean AC for effluents were 3.580, 0.082, 0.103, 0.063, and 0.090 Bq L-1 for Unat, 226Ra, 210Pb, 232Th, and 228Ra, respectively, for the total fraction. The analysis of variance pointed to Unat as a critical radionuclide, since it presented more than 90% of the total AC released into the environment. Pearson's R2 pointed to soluble fraction as a major contributor to the total AC released. The guidance level proposed by WHO was used to assess the radiological potability of the effluents. The results obtained indicated the need for trigger other analyses. Committed effective dose was estimated due to the unrestricted use of effluents and the value obtained, 0.23 mSv year-1, was below the maximum allowed limit. Finally, the radiotoxicity of the released effluent was evaluated and the value obtained was ~ 50% of the maximum allowed limit. In conclusion, the present study showed that the level of radioactivity released into the environment by the Ore Treatment Unit does not present a radiological risk to the surrounding population.

Acceptability and Feasibility of the Telehealth Bariatric Behavioral Intervention to Increase Physical Activity: Protocol for a Single-Case Experimental Study.

BACKGROUND: Regular physical activity (PA) is recommended to optimize weight and health outcomes in patients who have undergone metabolic and bariatric surgery (MBS). However, >70% of patients have low PA levels before MBS that persist after MBS. Although behavioral interventions delivered face-to-face have shown promise for increasing PA among patients who have undergone MBS, many may experience barriers, preventing enrollment into and adherence to such interventions. Delivering PA behavior change interventions via telehealth to patients who have undergone MBS may be an effective strategy to increase accessibility and reach, as well as adherence. OBJECTIVE: This paper reports the protocol for a study that aims to assess the feasibility and acceptability of the protocol or methods and the Telehealth Bariatric Behavioral Intervention (TELE-BariACTIV). The intervention is designed to increase moderate-to-vigorous intensity PA (MVPA) in patients awaiting bariatric surgery and is guided by a multitheory approach and a patient perspective. Another objective is to estimate the effect of the TELE-BariACTIV intervention on presurgical MVPA to determine the appropriate sample size for a multicenter trial. METHODS: This study is a multicenter trial using a repeated (ABAB'A) single-case experimental design. The A phases are observational phases without intervention (A1=pre-MBS phase; A2=length personalized according to the MBS date; A3=7 months post-MBS phase). The B phases are interventional phases with PA counseling (B1=6 weekly pre-MBS sessions; B2=3 monthly sessions starting 3 months after MBS). The target sample size is set to 12. Participants are inactive adults awaiting sleeve gastrectomy who have access to a computer with internet and an interface with a camera. The participants are randomly allocated to a 1- or 2-week baseline period (A1). Protocol and intervention feasibility and acceptability (primary outcomes) will be assessed by recording missing data, refusal, recruitment, retention, attendance, and attrition rates, as well as via web-based acceptability questionnaires and semistructured interviews. Data collected via accelerometry (7-14 days) on 8 occasions and via questionnaires on 10 occasions will be analyzed to estimate the effect of the intervention on MVPA. Generalization measures assessing the quality of life, anxiety and depressive symptoms, and theory-based constructs (ie, motivational regulations for PA, self-efficacy to overcome barriers to PA, basic psychological needs satisfaction and frustration, PA enjoyment, and social support for PA; secondary outcomes for a future large-scale trial) will be completed via web-based questionnaires on 6-10 occasions. The institutional review board provided ethics approval for the study in June 2021. RESULTS: Recruitment began in September 2021, and all the participants were enrolled (n=12). Data collection is expected to end in fall 2023, depending on the MBS date of the recruited participants. CONCLUSIONS: The TELE-BariACTIV intervention has the potential for implementation across multiple settings owing to its collaborative construction that can be offered remotely. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39633.

Mortality and risk of tuberculosis among people living with HIV in whom TB was initially ruled out.

Tuberculosis (TB) misdiagnosis remains a public health concern, especially among people living with HIV (PLHIV), given the high mortality associated with missed TB diagnoses. The main objective of this study was to describe the all-cause mortality, TB incidence rates and their associated risk factors in a cohort of PLHIV with presumptive TB in whom TB was initially ruled out. We retrospectively followed a cohort of PLHIV with presumptive TB over a 2 year-period in a rural district in Southern Mozambique. During the study period 382 PLHIV were followed-up. Mortality rate was 6.8/100 person-years (PYs) (95% CI 5.2-9.2) and TB incidence rate was 5.4/100 PYs (95% CI 3.9-7.5). Thirty-six percent of deaths and 43% of TB incident cases occurred in the first 12 months of the follow up. Mortality and TB incidence rates in the 2-year period after TB was initially ruled out was very high. The TB diagnostic work-up and linkage to HIV care should be strengthened to decrease TB burden and all-cause mortality among PLHIV with presumptive TB.

A standardized methodical approach to characterize the influence of key parameters on the in vitro efficacy of extracorporeal photopheresis.

Extracorporeal photopheresis (ECP) is an autologous immunomodulatory cell therapy that consists of the ex vivo collection of mononuclear cells (MNCs), which are irradiated with UVA in the presence of the photosensitizing agent 8-methoxypsoralen (8-MOP) to induce cell apoptosis. This photoactivated cell preparation is then reinfused into the patient. While the clinical benefits of ECP are well-demonstrated, no study has yet characterized the influence of variations in the composition of the cell preparation on the efficacy of ECP in vitro. Here, we describe a standardized methodology for the in vitro assessment of ECP that uses the human lymphoma T-cell line and mimics the clinical procedure. By quantifying cell apoptosis, inhibition of cell proliferation, and 8-MOP consumption, we used this approach to characterize the specific influence of key variables on the cellular response to ECP. We found that (i) increases in hematocrit and plasma concentrations attenuated the cellular response to ECP; (ii) plasma concentration was the only variable tested that influenced 8-MOP consumption; and (iii) the loss of efficacy due to variations in the concentration of certain blood components could be counteracted by modulating the UVA dose. This methodology may enable evaluation of other leukapheresis preparation protocols and better determination of the optimal working parameters for ECP.

Asparagine and sugars are both required to sustain secondary axis elongation after bud outgrowth in Rosa hybrida.

Nitrogen is required for optimal plant growth, especially in young organs such as secondary axes (axes II) after axillary bud outgrowth. Several studies have shown an increase of nitrogen concentration in xylem sap concomitantly with bud outgrowth, but the relation between nitrogen, sugars and plant hormones in axis II still remains unclear. We investigated in Rosa hybrida the involvement of nitrogen nutrition in axis II elongation in relation with sugars and cytokinins using 15N-labeled nitrate and sugars, amino acids and cytokinin quantifications. Besides, we measured the effect of the exogenous supply of these compounds on axis II elongation using in vitro excised bud culture. We demonstrated that nitrogen in the axis II comes mainly from new root uptake after decapitation. Asparagine, which concentration increases in sap exudates and tissues during axis II elongation, was the sole amino acid able to sustain an efficient elongation in vitro when supplied in combination with sucrose.

Structural, Microstructural, and Metabolic Alterations in Primary Progressive Aphasia Variants.

Neuroimaging studies have described the brain alterations in primary progressive aphasia (PPA) variants (semantic, logopenic, nonfluent/agrammatic). However, few studies combined T1, FDG-PET, and diffusion MRI techniques to study atrophy, hypometabolism, and tract alterations across the three PPA main variants. We therefore explored a large early-stage cohort of semantic, logopenic and nonfluent/agrammatic variants (N = 86) and of 23 matched healthy controls with anatomical MRI (cortical thickness), FDG PET (metabolism) and diffusion MRI (white matter tracts analyses), aiming at identifying cortical and sub-cortical brain alterations, and confronting these alterations across imaging modalities and aphasia variants. In the semantic variant, there was cortical thinning and hypometabolism in anterior temporal cortices, with left-hemisphere predominance, extending toward posterior temporal regions, and affecting tracts projecting to the anterior temporal lobes (inferior longitudinal fasciculus, uncinate fasciculus) and tracts projecting to or running nearby posterior temporal cortices: (superior longitudinal fasciculus, inferior frontal-occipital fasciculus). In the logopenic variant metabolic alterations were more extensive than atrophy affecting mainly the left temporal-parietal junction and extending toward more anterior temporal cortices. Metabolic and tract data were coherent given the alterations of the left superior and inferior longitudinal fasciculus and the left inferior frontal-occipital fasciculus. In the nonfluent/agrammatic variant cortical thinning and hypometabolism were located in the left frontal cortex but Broca's area was only affected on metabolic measures. Metabolic and tract alterations were coherent as reflected by damage to the left uncinate fasciculus connecting with Broca's area. Our findings provide a full-blown statistically robust picture of brain alterations in early-stage variants of primary progressive aphasia which has implications for diagnosis, classification and future therapeutic strategies. They demonstrate that in logopenic and semantic variants patterns of brain damage display a non-negligible overlap in temporal regions whereas they are substantially distinct in the nonfluent/agrammatic variant (frontal regions). These results also indicate that frontal networks (combinatorial syntax/phonology) and temporal networks (lexical/semantic representations) constitute distinct anatomo-functional entities with differential vulnerability to degenerative processes in aphasia variants. Finally, the identification of the specific damage patterns could open an avenue for trans-cranial stimulation approaches by indicating the appropriate target-entry into the damaged language system.

Effect of Surgical Intraocular Pressure Lowering on Peripapillary and Macular Vessel Density in Glaucoma Patients: An Optical Coherence Tomography Angiography Study.

PURPOSE: To measure the influence of surgically induced intraocular pressure lowering on peripapillary and macular vessel density in glaucoma patients using optical coherence tomography angiography. METHODS: Twenty-one eyes of 21 patients with open-angle glaucoma scheduled for filtering surgery were enrolled prospectively. Using optical coherence tomography angiography, vessel density was quantified within the peripapillary and macular regions, before and 1 month after filtering surgery. Change in vessel density was calculated for all analyzed areas. RESULTS: One month after surgery, the mean intraocular pressure reduction was 44.2%±4.8% (range, 15.2% to 77.1%). The mean change in vessel density for the whole peripapillary area was 0.065±0.88% (P=0.788). In the macular region, the mean change in vessel density was -0.022%±0.691% (P=0.405) with significant changes only within the inferotemporal area of patients with predominantly superior visual field defects (-1.86%±1.43%, P=0.024). CONCLUSIONS: Optical coherence tomography angiography allowed very limited measurement of intraocular pressure lowering-induced changes on the vessel density of the peripapillary and macular regions in glaucoma patients.

Optic Disc Vascularization in Glaucoma: Value of Spectral-Domain Optical Coherence Tomography Angiography.

Purpose. To detect changes in optic nerve head (ONH) vascularization in glaucoma patients using spectral-domain OCT angiography (OCT-A). Material and Method. Fifty glaucoma patients and 30 normal subjects were evaluated with OCT-A (AngioVue®, Optovue). The total ONH vessel density and temporal disc vessel density were measured. Clinical data, visual field (VF) parameters, and spectral-domain OCT evaluation (RNFL: retinal nerve fiber layer thickness, GCC: ganglion cell complex thickness, and rim area) were recorded for glaucoma patients. Correlations among total and temporal ONH vessel density and structural and VF parameters were analyzed. Results. In the glaucoma group, total and temporal ONH vessel density were reduced by 24.7% (0.412 versus 0.547; p < 0.0001) and 22.88% (0.364 versus 0.472; p = 0.001), respectively, as compared with the control group. Univariate analysis showed significant correlation between rim area (mm(2)) and temporal ONH vessel density (r = 0.623; p < 0.0001) and total ONH vessel density (r = 0.609; p < 0.0001). Significant correlations were found between temporal and total ONH vessel density and RNFL, GCC, VF mean deviation, and visual field index. Conclusion. In glaucoma patients OCT-A might detect reduced ONH blood vessel density that is associated with structural and functional glaucomatous damage. OCT-A might become a useful tool for the evaluation of ONH microcirculation changes in glaucoma.

Light and nitrogen nutrition regulate apical control in Rosa hybrida L.

Apical control is defined as the inhibition of basal axillary bud outgrowth by an upper actively growing axillary axis, whose regulation is poorly understood yet differs markedly from the better-known apical dominance. We studied the regulation of apical control by environmental factors in decapitated Rosa hybrida in order to remove the apical hormonal influence and nutrient sink. In this plant model, all the buds along the main axis have a similar morphology and are able to burst in vitro. We concentrated on the involvement of light intensity and nitrate nutrition on bud break and axillary bud elongation in the primary axis pruned above the fifth leaf of each rose bush. We observed that apical control took place in low light (92 µmol m(-2)s(-1)), where only the 2-apical buds grew out, both in low (0.25 mM) and high (12.25 mM) nitrate. In contrast, in high light (453 µmol m(-2)s(-1)), the apical control only operates in low nitrate while all the buds along the stem grew out when the plant was supplied with a high level of nitrate. We found a decreasing photosynthetic activity from the top to the base of the plant concomitant with a light gradient along the stem. The quantity of sucrose, fructose, glucose and starch are higher in high light conditions in leaves and stem. The expression of the sucrose transporter RhSUC2 was higher in internodes and buds in this lighting condition, suggesting an increased capacity for sucrose transport. We propose that light intensity and nitrogen availability both contribute to the establishment of apical control.

Differential regulation of two sucrose transporters by defoliation and light conditions in perennial ryegrass.

Sucrose transport between source and sink tissues is supposed to be a key-step for an efficient regrowth of perennial rye-grass after defoliation and might be altered by light conditions. We assessed the effect of different light regimes (high vs low light applied before or after defoliation) on growth, fructans and sucrose mobilization, as well as on sucrose transporter expression during 14 days of regrowth. Our results reported that defoliation led to a mobilization of C reserves (first sucrose and then fructans), which was parallel to an induction of LpSUT1 sucrose transporter expression in source and sink tissues (i.e. leaf sheaths and elongating leaf bases, respectively) irrespective to light conditions. Light regime (high or low light) had little effects on regrowth and on C reserves mobilization during the first 48 h of regrowth after defoliation. Thereafter, low light conditions, delaying the recovery of photosynthetic capacities, had a negative effect on C reserves re-accumulation (especially sucrose). Surprisingly, high light did not enhance sucrose transporter expression. Indeed, while light conditions had no effect on LpSUT1 expression, LpSUT2 transcripts levels were enhanced for low light grown plants. These results indicate that two sucrose transporter currently identified in Lolium perenne L. are differentially regulated by light and sucrose.

Toward optimal treatment in women: the effect of sex on metoprolol-diphenhydramine interaction.

The objective of this study was to determine if sex influences the pharmacokinetics and hemodynamics of the CYP2D6 substrate metoprolol and its interaction with diphenhydramine (CYP2D6 inhibitor) in healthy young participants with high (extensive metabolizer [EM]) or low (poor metabolizer [PM]) CYP2D6 activities. A prespecified comparative analysis of data from 2 sequential clinical trials that included 16 EM and 4 PM women and 10 EM and 6 PM men was performed. The participants in the 2 trials were administered a single oral dose of 100 mg metoprolol in the presence of steady-state diphenhydramine or placebo. Serial plasma and urine samples were obtained for 48 hours, and hemodynamic data was obtained for 12 hours after metoprolol. In the placebo arm, EM and PM women had 62% and 59% higher S-metoprolol AUC(0-infinity) and 26% and 71% lower CL/F, respectively, compared to men with the same phenotype (all Ps < .05 women compared to men). These differences dissipated on body weight (WT) correction. Women (especially PMs) experienced greater negative chronotropic effects of metoprolol than men (P < .0001 women compared to men). Diphenhydramine coadministration increased S-metoprolol AUC by 84% in EM women and 45% in EM men (P < .009 women compared to men). In the diphenhydramine arm, sex differences in pharmacokinetics persisted even after WT correction, resulting in greater negative chronotropic effects in women (all Ps < .05 women compared to men). Metoprolol dose should be adjusted for body weight, particularly in women. Coadministration of a CYP2D6 inhibitor such as diphenhydramine, by a patient at similar doses in the 2 sexes, could result in a greater inhibition of clearance of CYP2D6 substrates with a resulting higher risk of pronounced pharmacological and adverse effects in women compared to men.

Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans.

CYP1A2 is involved in the metabolism of both caffeine and propafenone, a class Ic antiarrhythmic agent. Despite the widespread consumption of caffeine, drug-drug interactions with this agent are often overlooked. This study investigated effects of propafenone on the pharmacokinetics of caffeine. Eight healthy volunteers were included in our study. A total of 300 mg of caffeine was given on 2 occasions, once alone and once during the coadministration of 300 mg propafenone. Serial blood samples were collected and pharmacokinetic parameters were estimated using a population pharmacokinetic approach. A one-compartment PK model with first-order absorption and elimination described plasma concentration profiles. Concomitant administration of propafenone decreased caffeine oral clearance from 8.3 +/- 0.9 L/h to 5.4 +/- 0.7 L/h (P < 0.05). Elimination half-life of caffeine was also increased 54% by propafenone. One of our volunteers was a poor metabolizer of CYP2D6. Concomitant administration of propafenone to this volunteer caused the greatest increase in caffeine plasma concentrations. These results support the concept of competitive inhibition between propafenone and caffeine. Our results suggest that propafenone causes significant inhibition of CYP1A2 activity leading to a decrease in the clearance of caffeine. Caffeine has intrinsic proarrhythmic effects; thus, its coadministration with an antiarrhythmic agent such as propafenone should be used with caution, especially in patients with poor CYP2D6 activity.

Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women.

Premenopausal women may be most vulnerable to acute coronary syndromes at a point in their menstrual cycle when their plasma estrogen levels are the lowest during and immediately after menstruation. Metoprolol is a first-line drug in the management of patients with acute coronary syndrome; however, when metoprolol was marketed in 1982, women were largely excluded from clinical trials. Furthermore, the over-the-counter antihistamine diphenhydramine inhibited the metabolism of the CYP2D6 substrate metoprolol in healthy, young men with pharmacokinetic and pharmacodynamic consequences. The pharmacokinetics and pharmacodynamics of metoprolol and its interaction with diphenhydramine were investigated in a randomized, double-blind, crossover, placebo-controlled manner in healthy, premenopausal extensive (EM; n = 16) and poor metabolizer (PM; n = 4) women immediately after menstruation. During the placebo phase, EMs had between 5.2- and 8.4-fold higher total clearance (CL/F) of R- and S-metoprolol compared with PMs, whereas the latter had a 35% greater area under the effect curve (AUEC) and 60% greater EC(50) value for heart rate reduction than EMs (all P < 0.05). Diphenhydramine coadmininstration caused a 2.2- to 3.2-fold decrease in CL/F of metoprolol enantiomers with a resulting 21% increase in AUEC and 29% increase in EC(50) value for heart rate reduction in EMs (all P < 0.05). This is the first study to report an in-depth elucidation of metoprolol's pharmacokinetics and hemodynamics in premenopausal EM and PM women at a point in their menstrual cycle when vulnerability for acute coronary events may be greatest. Caution is warranted when the over-the-counter antihistamine diphenhydramine is part of a chronic therapeutic regimen.