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The quality assessment of medicines involves multiple compliance parameters, such as identity, dosage, purity, potency, content uniformity, disintegration time, dissolution rate, among others. The measurement uncertainty associated with a measured value can affect the conformity assessment and, consequently, it impacts decision-making. Even if the particular risks are acceptable, the total risk may be significantly high. Thus, the aim of this work was to develop a procedure for the definition of acceptance (or rejection) limits applied to multiple compliance assessments, that ensure acceptable particular and total risks. The multiple compliance assessments were performed and applied in the pharmaceutical equivalence studies for cisplatin injectable solution, carboplatin injectable solution, ranitidine tablets, and acetaminophen oral solution from several manufacturers. Pharmaceutical equivalence studies were performed adopting pharmacopeial analytical procedures. All chromatographic system suitability results complied with the requirements regarding the resolution between peaks, the capacity factor, the tailing factor, the theoretical plates, and the relative standard deviation for replicate injections. Univariate and multivariate guard-bands (g and g', respectively) were calculated by multiplying the standard uncertainty (u) by an appropriate univariate and multivariate coverage factor (k and k', respectively).The values of multivariate guard band (g') were higher than the values of univariate guard bands (g), which leads to more restrictive acceptance intervals. Measured values between the conventional and the multivariate acceptance limits will ensure particular risk values below the maximum acceptable value, however, the total risk may be significantly high. On the other hand, measured values within the multivariate acceptance limits ensure that particular risk values and total risk value are below the maximum acceptable value The application of multivariate guard bands is a simple way to ensure reduced particular and total risks of false conformity decisions, which is of great interest to regulatory agencies and the manufactures of the medicines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This global study, which has been coordinated by the World Meteorological Organization Global Atmospheric Watch (WMO/GAW) programme, aims to understand the behaviour of key air pollutant species during the COVID-19 pandemic period of exceptionally low emissions across the globe. We investigated the effects of the differences in both emissions and regional and local meteorology in 2020 compared with the period 2015-2019. By adopting a globally consistent approach, this comprehensive observational analysis focuses on changes in air quality in and around cities across the globe for the following air pollutants PM 2.5 , PM 10 , PMC (coarse fraction of PM), NO 2 , SO 2 , NOx, CO, O 3 and the total gaseous oxidant (OX = NO 2  + O 3 ) during the pre-lockdown, partial lockdown, full lockdown and two relaxation periods spanning from January to September 2020. The analysis is based on in situ ground-based air quality observations at over 540 traffic, background and rural stations, from 63 cities and covering 25 countries over seven geographical regions of the world. Anomalies in the air pollutant concentrations (increases or decreases during 2020 periods compared to equivalent 2015-2019 periods) were calculated and the possible effects of meteorological conditions were analysed by computing anomalies from ERA5 reanalyses and local observations for these periods. We observed a positive correlation between the reductions in NO 2 and NOx concentrations and peoples' mobility for most cities. A correlation between PMC and mobility changes was also seen for some Asian and South American cities. A clear signal was not observed for other pollutants, suggesting that sources besides vehicular emissions also substantially contributed to the change in air quality. As a global and regional overview of the changes in ambient concentrations of key air quality species, we observed decreases of up to about 70% in mean NO 2 and between 30% and 40% in mean PM 2.5 concentrations over 2020 full lockdown compared to the same period in 2015-2019. However, PM 2.5 exhibited complex signals, even within the same region, with increases in some Spanish cities, attributed mainly to the long-range transport of African dust and/or biomass burning (corroborated with the analysis of NO 2 /CO ratio). Some Chinese cities showed similar increases in PM 2.5 during the lockdown periods, but in this case, it was likely due to secondary PM formation. Changes in O 3 concentrations were highly heterogeneous, with no overall change or small increases (as in the case of Europe), and positive anomalies of 25% and 30% in East Asia and South America, respectively, with Colombia showing the largest positive anomaly of ~70%. The SO 2 anomalies were negative for 2020 compared to 2015-2019 (between ~25 to 60%) for all regions. For CO, negative anomalies were observed for all regions with the largest decrease for South America of up to ~40%. The NO 2 /CO ratio indicated that specific sites (such as those in Spanish cities) were affected by biomass burning plumes, which outweighed the NO 2 decrease due to the general reduction in mobility (ratio of ~60%). Analysis of the total oxidant (OX = NO 2  + O 3 ) showed that primary NO 2 emissions at urban locations were greater than the O 3 production, whereas at background sites, OX was mostly driven by the regional contributions rather than local NO 2 and O 3 concentrations. The present study clearly highlights the importance of meteorology and episodic contributions (e.g., from dust, domestic, agricultural biomass burning and crop fertilizing) when analysing air quality in and around cities even during large emissions reductions. There is still the need to better understand how the chemical responses of secondary pollutants to emission change under complex meteorological conditions, along with climate change and socio-economic drivers may affect future air quality. The implications for regional and global policies are also significant, as our study clearly indicates that PM 2.5 concentrations would not likely meet the World Health Organization guidelines in many parts of the world, despite the drastic reductions in mobility. Consequently, revisions of air quality regulation (e.g., the Gothenburg Protocol) with more ambitious targets that are specific to the different regions of the world may well be required., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the relationship between the presence of symptoms of anxiety or depression with breathing pattern and thoracoabdominal mechanics at rest and during exercise in COPD., Methods: Cross-sectional study enrolled 54 patients with COPD ranked according to Hospital Anxiety and Depression Scale (HAD) score and compared to dyspnea, clinical control, hypercapnia, breathing pattern and thoracoabdominal mechanics at rest and during exercise., Results: Seventeen patients with COPD had no symptoms, 12 had anxiety symptoms, 13 had depressive symptoms and 12 had both symptoms. COPD with depressive symptoms presented greater degree of dyspnea (p<0.01). Poor clinical control was observed in COPD with anxious and/or depressive symptoms (p<0.05). Breathing pattern and thoracoabdominal mechanics were similar among all groups at rest and during exercise., Conclusions: COPD with symptoms of depression report more dyspnea. Anxiety and depression are associated with poor clinical control without impact on breathing pattern and thoracoabdominal mechanics in COPD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The developmental effect of altered 5-HT and NE levels is a subject that requires more attention, especially when considering the increased demand for antidepressive dual reuptake inhibitors. Serotonin and norepinephrine are bioamines that differentially influence the nervous tissue growth. This study investigated the somatic maturation and the ontogeny of reflexes in neonate rats treated from the 1st to the 21st postnatal day (PND) with clomipramine (20 mg/kg sc, daily), a potent monoamine reuptake inhibitor. Indicators of both general body growth (body weight, axis of the head and body lengths) and physical maturation (ear unfolding, auditory conduit opening, eruption of the lower incisors and eye opening) were appraised. Ontogeny of motor and sensory reflexes (righting, free-fall righting--acceleration, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing) was also observed. The results demonstrated that chronic neonatal treatment with clomipramine alters the somatic growth. However, it did not interfere with the onset time of many physical features and reflexes. These results provide insights into the consequences of dual transmitter during early development.

Objectives: Characterization of beta-galactosidase in leukocytes and fibroblasts of heterozygotes for GM1 type I., Design and Methods: Leukocyte and fibroblast beta-galactosidase activity was determined fluorimetrically using 4-methylumbelliferyl-beta-D-galactoside as an artificial substrate. Optimum pH, Km, Vmax and thermostability of the enzyme at 42 degrees C were determined., Results: The leukocyte and fibroblast enzyme of heterozygotes have an optimum pH of 4.0 and 4.2, respectively. In normal subjects, the optimum pH was 4.2 in both cells, according to previous studies. The Km of the enzyme of heterozygotes was determined to be 0.65 mM in leukocytes and 0.59 mM in fibroblasts. The Vmax was determined in 167.21 nmol/h/mg of protein in heterozygotes leukocytes and 541.2 nmol/h/mg of protein in heterozygotes fibroblasts compared to 291.7 and 1768.1 nmol/h/mg of protein in controls leukocytes and fibroblasts, respectively. When leukocyte and fibroblast heterozygote beta-galactosidase was preincubated at 42 degrees C, after 80 min the residual activity was determined to be 25 to 30% of the initial activity. These results are similar to the control group., Conclusions: We have found significant differences between the two groups in some investigated parameters. Both fibroblasts and leukocytes showed a virtually similar level of reliability as source of enzyme for the detection of heterozygotes.