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For the first time, alumina functionally graded materials (FGMs) with additions of niobium oxide, lithium fluoride and zirconia were produced by spark plasma sintering (SPS) and their sintering behaviour and dynamic properties were studied aiming to evaluate possibility of their use as ballistic shielding. Six groups of alumina samples with different layer compositions were produced by SPS at 1400 °C/5min. The samples were characterized by dilatometry, scanning electron microscopy (SEM) and Hopkinson split bar method. The composition with the zirconia addition exhibited lower shrinkage rates at higher temperatures than the groups without zirconia, which promoted small sample shrinkage, resulting in lower density and higher porosity. The dynamic test showed that the alumina FGMs with layer containing LiF had the highest strain and strain rate values, exhibiting that the presence of continuous gradients in the composition positively affects the ceramic properties. Densification, layer change and cracks propagating through the material layers were also analysed by SEM analyses.

Cristina Monteiro,1 Catarina Canário,2,3 Manuel Ângelo Ribeiro,3 Ana Paula Duarte,1,2 Gilberto Alves1,2 1UFBI – Pharmacovigilance Unit of Beira Interior, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal; 2CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; 3Associação de Socorros Mútuos-Mutualista Covilhanense, Covilhã, PortugalCorrespondence: Cristina MonteiroUFBI – Pharmacovigilance Unit of Beira Interior, Faculty of Health Sciences, University of Beira Interior, Covilhã 6200-506, PortugalTel +35 1275329070Email csjmonteiro79@gmail.comPurpose: The increase in drug prescription for the elderly raises the risk of the occurrence of potentially inappropriate medications (PIMs), thus increasing the incidence of drug-related problems. Likewise, potential prescribing omissions (PPOs) are also highly prevalent in the elderly. This study aimed at assessing the prevalence of PIMs in the elderly by using the EU(7)-PIM list, STOPP criteria version 2 and the Beers criteria version 2015, as well as the prevalence of PPOs by applying the START criteria version 2 in elderly nursing home residents and outpatients of the Eastern Central Region of Portugal.Patients and Methods: A descriptive cross-sectional study was carried out in a sample of 90 Portuguese elderly people. Age, gender, diagnoses and medication history were collected from the patients’ clinical records. The prevalence of PIMs and PPOs was measured according to each of the criteria applied.Results: The patients’ ages ranged from 65 to 103 years, with an average age of 84.15 years. In addition, the average number of medications prescribed was 7.6. The STOPP criteria identified 250 PIMs affecting 77 patients (85.5%), the EU(7)-PIM list detected 94 PIMs in 58 patients (64.4%) and the Beers criteria identified 69 PIMs in 51 patients (56.6%). Therefore, the STOPP criteria version 2 identified substantially more PIMs than the other two tools. Furthermore, by applying the START criteria 68 PPOs were detected in 52 patients (57.7%).Conclusion: A high prevalence of PIMs and PPOs was observed, suggesting the need to implement actions aimed at reducing the phenomenon and thus help to improve the quality of care provided in nursing homes. The variations in prevalence with the different tools suggest the need to carefully choose the tool for medication review in the elderly.Keywords: potentially inappropriate medications, potential prescribing omissions, EU(7)-PIM list, STOPP/START criteria version 2, Beers criteria version 2015, elderly

Climate change may be considered relevant for hydropower production schemes all over the world. Despite this, the assessment of the impact of climate change on hydropower is uncertain and must be interpreted with that in mind. The paper focuses on the Namakhvani HPP (400 MW), a new project under development in the Rioni River, in Georgia. Using it as an example, the paper emphasizes the critical role that is played by uncertainty in climate impact risk assessments and explores the interpretation of simulation results, providing ways in which they can be transformed in actionable information for decision-making.

The recent development of Electrical Submersible Pump (ESP) in the skid, installed in the seabed downstream of the wellhead in an offshore oil production system, is an alternative to the conventional system with the set installed at the bottom of the producing well, facilitating interventions in case of failure. The pump is driven by an electric motor whose cooling must be efficient to ensure the continuity of its operation. The heat withdrawal is performed by the fluid produced. The purpose of this article is to understand the process of electric motor cooling to the single-phase and turbulent flow with convection heat transfer in an annular geometry, which represents the space formed between a capsule and the ESP in the Skid system motor. With this objective it is employed a Computational Fluid Dynamics (CFD) code to solve the governing equations of the turbulent heat transfer single-phase flow. The standard κ-ε model with improved wall function (Enhanced Wall Treatment) is used to closure turbulence problem. This study considered flow rates range of 2200–4200 m3/d (representing Reynolds numbers range of 27 000–133 000 approximately), Prandtl numbers 7–37, three configurations of different annular geometries, one concentric and two eccentric, together with the condition of the constant temperature on the motor surface (130 °C) and capsule (4 °C). The simulations are validated by comparing the Nusselt number in the developed region with the Gnielinski correlation. It is observed that if the constant heat flux condition were used, the motor temperature would have lower values at the beginning and larger at the end of the geometry. Therefore, the higher the Nusselt number, the greater the heat transfer, thus intensifying the cooling of the electric motor. In the eccentric geometry a momentum transfer from the lower to the upper annular region is observed, causing the Nusselt number present an angular variation. In eccentric geometries the flow develops in greater lengths, observing that the greater the eccentricity, the greater this length. Finally, for the ESP in the Skid system the use of an eccentric geometry is not adequate.

Purpose: Climate change is one of the direst health threats that humanity faces. We aim to estimate the carbon dioxide (CO2) emissions associated with the energy usage from linear accelerator (LINAC)-based external beam radiation therapy (EBRT) for the most common cancer diagnoses. Methods and Materials: We identified patients with the 4 most common cancer types treated with curative-intent EBRT. Beam-on time for each fraction was extracted from the treatment planning system and averaged over each site and treatment modality. The power was multiplied by the beam-on time in hours to yield kilowatt hours (kWh). Using the US Environmental Protection Agency Greenhouse Gas Equivalencies calculator, we converted the kWh into estimates of CO2-equivalent emissions for the average US power grid. Idle time of the LINAC was estimated via Varian Medical Systems. Results: A total of 10 patients were included for each of the following modalities: conventionally fractionated for prostate cancer (28 fractions [fx]), prostate stereotactic body radiation therapy (SBRT) (5 fx), 15- and 5-fx regimens for early-stage breast cancer, 3- and 5-fx SBRT regimens for early-stage lung cancer, conventional EBRT (30 fx) for locally advanced lung cancer, and short- (5 fx) and long-course (25-28 fx) for rectal cancer. The modality with the lowest and highest carbon emissions per course, on average, was prostate SBRT (2.18 kg CO2; interquartile range, 1.92-2.30) and conventional treatment for prostate cancer (17.34 kg CO2; interquartile range, 10.26-23.79), respectively. This corresponds to CO2-equivalent emissions of driving an average of 5.4 miles and 41.2 miles in a standard vehicle, respectively. “Standby” mode for a LINAC TrueBeam and Clinac IX uses 112 kWh and 64.8 kWh per day, respectively. Conclusions: We have estimated CO2 emissions arising from direct energy usage of a LINAC for 4 common cancers treated with EBRT. “Standby” mode of a LINAC uses the most energy per day. Comprehensive studies are warranted to minimize the environmental effects of health and cancer care.

Objectives: This in vitro study focused on verifying the influence of different ambient light conditions on the accuracy and precision of models obtained from digital scans., Methodology: To measure the tested illuminances: chair light/reflector; room light, and natural light at the time of scanning, a luxmeter was used. From the STL file, nine experimental groups were formed., Results: Of the nine specific combinations between the three IOS and the three types of lighting, it was verified that for all of them, as well as the ICC, the accuracy was also excellent, in which the measured values were not significantly influenced by the IOS brand (p = 0.994) nor by the type of lighting (p = 0.996). For precision data, GLM indicated a statistically significant interaction between IOS and lighting type. Under LS, accuracy was significantly higher with 3Shape® than with CS 3600 CareStream®, which had significantly higher accuracy than Virtuo Vivo™ Straumann®., Conclusions: The models obtained with the three IOS evaluated exhibited excellent accuracy under the different illuminance tested and the 3Shape® under the three illuminance conditions was the device that presented the best precision, specifically when using LC and LS., (Copyright© 2024 Dennis Barber Ltd.)

Biliary complications like cholelithiasis and choledocholithiasis are more common in bariatric surgery patients due to obesity and rapid weight loss. Patients with a body mass index > 40 face an eightfold risk of developing cholelithiasis. Post-bariatric surgery, especially after laparoscopic Roux-en-Y gastric bypass (LRYGB), 30% of patients develop biliary disease due to rapid weight loss. The aim of this review is to analyze the main biliary complications that occur after bariatric surgery and its management. A review of the literature was conducted mainly from 2010 up to 2023 with regard to biliary complications associated with bariatric patients in SciELO, PubMed, and MEDLINE. Patients undergoing LRYGB have a higher incidence (14.5%) of symptomatic calculi post-surgery compared to those undergoing laparoscopic sleeve gastrectomy at 4.1%. Key biliary complications within 6 to 12 months post-surgery include: Cholelithiasis: 36%; Biliary colic/dyskinesia: 3.86%; Acute cholecystitis: 0.98%-18.1%; Chronic cholecystitis: 70.2%; Choledocholithiasis: 0.2%-5.7% and Pancreatitis: 0.46%-9.4%. Surgeons need to be aware of these complications and consider surgical treatments based on patient symptoms to enhance their quality of life., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A silent spread of human T cell lymphotropic virus type 1 (HTLV-1) has been occurring for thousands of years, with a high prevalence in some regions due to the sexual and vertical transmission and formation of family clusters. The time from HTLV-1 infection until the onset of virus-associated diseases is extremely long, approximately one to three decades. In this study, we evaluated intrafamilial HTLV-1 transmission and associated diseases in 1,204 individuals enrolled and followed up by the GIPH cohort between 1997 and 2017. The family groups ( n  = 43) were composed of 279 individuals who were tested for HTLV-1/human T cell lymphotropic virus type 2 (HTLV-2) and were classified as two groups according to the index case: blood donor (blood donors referred to the GIPH cohort) and nondonor (individuals referred to the GIPH cohort by other health services). The observed rates of HTLV-1 transmission and associated diseases among the relatives were high. Of 236 family members and sexual partners tested for HTLV, 104 (44.1%) were confirmed as having HTLV infection, with 36.7% of relatives whose index case was blood donors and 56.9% of relatives with nondonor index cases. At least one case of HTLV-1-associated myelopathy was observed in 42.9% of the families with intrafamilial transmission of HTLV-1. Brazil is an endemic area for HTLV-1/2 and has implemented mandatory universal screening of blood donors for HTLV-1/2 since 1993. However, the lack of public health services offer diagnosis for HTLV to the general population and pregnant women in the country makes it difficult to identify infected people, and contributes to the silent spread of the virus.

Objective: It is known that exposure to air pollution is associated with an increased risk for cardiovascular and respiratory diseases. This review aimed to summarise observational studies on the impact of short and long-term exposure to ambient air pollution on prevalence of hospitalisations and/or emergency department visits caused by respiratory diseases in children and adolescents., Sources: Pubmed, Scopus, Embase and Cochrane Library databases were searched for the years 2018 to December 2022, including studies in any language., Summary of the Findings: A total of 15 studies published between 2018 and 15 January 2022 were included in this review. PM 2.5 was the most type of particulate matter studied. Short-term exposure to PM 2,5 , PM 10 , NO 2 , SO 2 and O 3 , even at concentrations less than the current health-based guidelines, was significantly correlated with increased risk of outpatient/hospital visits and hospitalisations for respiratory diseases by children., Conclusions: Our findings emphasise the importance and urgency of long-term control of air pollution and pollution-related diseases, especially among children and adolescents. There is a need for further research employing more homogeneous methodologies for assessing exposure and outcome measurements, in order to enable systematic reviews with meta-analysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Primary biliary tract tumors are malignancies that originate in the liver, bile ducts, or gallbladder. These tumors often present with jaundice of unknown etiology, leading to delayed diagnosis and advanced disease. Currently, several palliative treatment options are available for primary biliary tract tumors. They include percutaneous transhepatic biliary drainage (PTBD), biliary stenting, and surgical interventions such as biliary diversion. Systemic therapy is also commonly used for the palliative treatment of primary biliary tract tumors. It involves the administration of chemotherapy drugs, such as gemcitabine and cisplatin, which have shown promising results in improving overall survival in patients with advanced biliary tract tumors. PTBD is another palliative treatment option for patients with unresectable or inoperable malignant biliary obstruction. Biliary stenting can also be used as a palliative treatment option to alleviate symptoms in patients with unresectable or inoperable malignant biliary obstruction. Surgical interventions, such as biliary diversion, have traditionally been used as palliative options for primary biliary tract tumors. However, biliary diversion only provides temporary relief and does not remove the tumor. Primary biliary tract tumors often present in advanced stages, making palliative treatment the primary option for improving the quality of life of patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Studies have shown an increased risk of morbidity in elderly patients suffering rib fractures from blunt trauma. The association between frailty and rib fractures on adverse outcomes is still ill-defined. In the current investigation, we sought to delineate the association between frailty, measured using the Orthopedic Frailty Score (OFS), and outcomes in geriatric patients with isolated rib fractures., Methods: All geriatric (aged 65 years or older) patients registered in the 2013-2019 Trauma Quality Improvement database with a conservatively managed isolated rib fracture were considered for inclusion. An isolated rib fracture was defined as the presence of ≥1 rib fracture, a thorax Abbreviated Injury Scale (AIS) between 1 and 5, an AIS ≤1 in all other regions, as well as the absence of pneumothorax, hemothorax, or pulmonary contusion. Based on patients' OFS, patients were classified as non-frail (OFS 0), pre-frail (OFS 1), or frail (OFS ≥2). The prevalence ratio (PR) of composite complications, in-hospital mortality, failure-to-rescue (FTR), and intensive care unit (ICU) admission between the OFS groups was determined using Poisson regression models to adjust for potential confounding., Results: A total of 65 375 patients met the study's inclusion criteria of whom 60% were non-frail, 29% were pre-frail, and 11% were frail. There was a stepwise increased risk of complications, in-hospital mortality, and FTR from non-frail to pre-frail and frail. Compared with non-frail patients, frail patients exhibited a 87% increased risk of in-hospital mortality [adjusted PR (95% CI): 1.87 (1.52-2.31), p<0.001], a 44% increased risk of complications [adjusted PR (95% CI): 1.44 (1.23-1.67), p<0.001], a doubling in the risk of FTR [adjusted PR (95% CI): 2.08 (1.45-2.98), p<0.001], and a 17% increased risk of ICU admission [adjusted PR (95% CI): 1.17 (1.11-1.23), p<0.001]., Conclusion: There is a strong association between frailty, measured using the OFS, and adverse outcomes in geriatric patients managed conservatively for rib fractures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Repeated exposure to psychosocial stress modulates the endocannabinoid system, particularly anandamide (AEA) signaling in brain regions associated with emotional distress. The mTOR protein regulates various neuroplastic processes in the brain disrupted by stress, including adult hippocampal neurogenesis. This kinase has been implicated in multiple effects of cannabinoid drugs and the anti-stress behavioral effects of psychoactive drugs. Therefore, our hypothesis is that enhancing AEA signaling via pharmacological inhibition of the fatty acid amide hydrolase (FAAH) enzyme induces an anti-stress behavioral effect through an mTOR-dependent mechanism. To test this hypothesis, male C57Bl6 mice were exposed to social defeat stress (SDS) for 7 days and received daily treatment with either vehicle or different doses of the FAAH inhibitor, URB597 (0.1; 0.3; 1 mg/Kg), alone or combined with rapamycin. The results suggested that URB597 induced an inverted U-shaped dose-response curve in mice subjected to SDS (with the intermediate dose of 0.3 mg/kg being anxiolytic, and the higher tested dose of 1 mg/Kg being anxiogenic). In a second independent experiment, rapamycin treatment induced an anxiogenic-like response in control mice. However, in the presence of rapamycin, the anxiolytic dose of URB597 treatment failed to reduce stress-induced anxiety behaviors in mice. SDS exposure altered the hippocampal expression of the mTOR scaffold protein Raptor. Furthermore, the anxiogenic dose of URB597 decreased the absolute number of migrating doublecortin (DCX)-positive cells in the dentate gyrus, suggesting an anti-anxiety effect independent of newly generated/immature neurons. Therefore, our results indicate that in mice exposed to repeated psychosocial stress, URB597 fails to counteract the anxiogenic-like response induced by the pharmacological dampening of mTOR signaling., 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 © 2023 Elsevier B.V. All rights reserved.)

Ethical review systems need to build on their experiences of COVID-19 research to enhance their preparedness for future pandemics. Recommendations from representatives from over twenty countries include: improving relationships across the research ecosystem; demonstrating willingness to reform and adapt systems and processes; and making the case robustly for better resourcing., (© 2023. © World Health Organization 2023.)

Advice from multiple stakeholders is required to design the optimal pediatric clinical trial. We present recommendations for acquiring advice from trial experts and patients/caregivers, derived from advice meetings that were performed through a collaboration of the Collaborative Network for European Clinical Trials for Children (c4c) and the European Patient-CEntric ClinicAl TRial PLatforms (EU-PEARL). Three advice meetings were performed: (1) an advice meeting for clinical and methodology experts, (2) an advice meeting for patients/caregivers, and (3) a combined meeting with both experts and patients/caregivers. Trial experts were recruited from c4c database. Patients/caregivers were recruited through a patient organization. Participants were asked to provide input on a trial protocol, including endpoints, outcomes, and the assessment schedule. Ten experts, 10 patients, and 13 caregivers participated. The advice meetings resulted in modification of eligibility criteria and outcome measures. We have provided recommendations for the most effective meeting type per protocol topic. Topics with limited options for patient input were most efficiently discussed in expert advice meetings. Other topics benefit from patient/caregiver input, either through a combined meeting with experts or a patients/caregivers-only advice meeting. Some topics, such as endpoints and outcome measures, are suitable for all meeting types. Combined sessions profit from synergy between experts and patients/caregivers, balancing input on protocol scientific feasibility and acceptability. Both experts and patients/caregivers provided critical input on the presented protocol. The combined meeting was the most effective methodology for most protocol topics. The presented methodology can be used effectively to acquire expert and patient feedback., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Several pieces of evidence suggest that the monoaminergic theory of depression cannot fully explain all behavioral and neuroplastic changes observed after antidepressant chronic treatment. Other molecular targets, such as the endocannabinoid system, have been associated with the chronic effects of these drugs. In the present study, we hypothesized that the behavioral and neuroplastic effects observed after repeated treatment with the antidepressants (AD) Escitalopram (ESC) or venlafaxine (VFX) in chronically stressed mice depend on CB1 receptor activation. Male mice submitted to the chronic unpredictable stress (CUS) paradigm for 21 days were treated with Esc (10 mg/kg) or VFX (20 mg/kg) once a day in the presence or not of AM251 (0.3 mg/kg), a CB 1 receptor antagonist/inverse agonist. At the end of the CUS paradigm, we conducted behavior tests to evaluate depressive- and anxiety-like behaviors. Our results demonstrated that chronic blockade of the CB 1 receptor does not attenuate the antidepressant- or the anxiolytic-like effects of ESC nor VFX. ESC increased the expression of CB 1 in the hippocampus, but AM251 did not change the pro-proliferative effects of ESC in the dentate gyrus or the increased expression of synaptophysin induced by this AD in the hippocampus. Our results suggest that CB 1 receptors are not involved in behavioral and hippocampal neuroplastic effects observed after repeated antidepressant treatment in mice submitted to CUS., Competing Interests: Declaration of Competing Interest Neither of the authors has any conflict of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Despite higher sperm DNA fragmentation may affect intracytoplasmic sperm injection (ICSI) outcomes, sperm selection protocols do not evaluate this parameter. Therefore, sperm's head birefringence has been suggested as an adjuvant of seminal processing to select viable sperm for couples with severe male factor. Considering men with normal seminal parameters may also curse with DNA fragmentation, the aim of this study was to evaluate the impact of sperm selection by birefringence on ICSI outcomes in couples with different infertility factors compared to those submitted to conventional sperm selection., Methods: In this case-control study, medical records from 181 couples who underwent ICSI from January 2018 to August 2020 (107 from the Conventional and 74 from the Birefringence group) were included in the study. Clinical characteristics and ICSI outcomes were compared between the groups using Student's t test or Chi-square test (p<0.05) and a multivariate logistic regression model was applied regarding clinical pregnancy., Results: Despite the Birefringence group showed higher female age (p=0.01), lower seminal sperm concentration (p<0.01) and higher sperm DNA fragmentation (p<0.01), those patients cursed with both higher cleavage rate (p=0.04), clinical pregnancy rate per transfer (p=0.03) and clinical pregnancy rate per initiated cycle (p=0.02). The logistic regression showed a positive group effect on clinical pregnancy., Conclusions: The findings suggest a positive clinical impact of this cheap and easily reproducible adjuvant technique on ICSI outcomes in couples with different infertility factors. If confirmed by further methodologically appropriate studies, the sperm's head birefringence could be considered to improve the reproductive chances of those patients.

Purpose: Clinical education is an essential part of the Dental School curriculum and assessment is a fundamental component of the teaching-learning process., Objectives: With the purpose of implementing a structured and objective assessment method in the teaching of Oral Radiology, undergraduate dentistry students were submitted to an assessment of clinical competences and skills in radiology by the Objective Structured Clinical Examination (OSCE), applied both in-person and virtually (VOSCE)., Methods: The same group of students was evaluated by the OSCE and VOSCE in six-station circuits that involved the assessment of clinical skills in Oral Radiology. For each station, an individual evaluative checklist (per station) was prepared and the participants' general scores were obtained. The students' anxiety level was also assessed before and after the exams and a meta-evaluation was performed to indicate the participants' perception of the assessment methods., Results: The OSCE (0.61) and VOSCE (0.81) reliability values were considered substantial and almost perfect, respectively. The students evaluated showed a better performance in the OSCE (p ≤ 0.05). Anxiety levels were considered moderate in both assessments and showed no difference between the two exams. The meta-evaluation showed a positive evaluation for the items "time of execution", "clarity", "degree of difficulty" and "importance for clinical practice", both for the OSCE and the VOSCE., Conclusions: The OSCE was effective for evaluating clinical competencies and skills in Oral Radiology, both in face-to-face and virtual examinations, but with a limitation in the online method for evaluating technical skills., (© 2022 American Dental Education Association.)

To investigate a 12-year historical series (2006-2017) of human T-cell lymphotropic virus (HTLV)-positive blood donations from Fundação Hemominas, Minas Gerais, Brazil, an observational retrospective study was performed to evaluate data of blood donor candidates who were screened for HTLV-1/2 by enzyme-linked immunosorbent assay or chemiluminescence assays and confirmed by Western blot. We analyzed 3 309 716 blood donations covering 2006-2017 that were extracted from the institutional database. In a total of 3 308 738 donations that have complete algorithm tests, the global frequency of HTLV-positive donations was 0.012%. The seroprevalence in first-time blood donors was 28.82/100 000 donors; 0.95/100 000 donations were HTLV-positive in repeat blood donors. The frequency of HTLV-seropositive females was significantly higher than males (odds ratio = 1.85, p < 0.001) in first-time donors. The median age of HTLV-positive first-time and repeat donors was similar (36 and 32 years, respectively). First-time donors ≥41 years had higher odds to be infected. There was a clear tendency of decline in the HTLV-positive donations in the period analyzed, going from 19.26/100 000 donations to 8.50/100 000 donations. The increase in the proportion of repeat donors over the period analyzed (from 23% in 2006 to 67% in 2017) must be the principal factor that contributed to this drop. Our results showed a continuous decline in the frequency of HTLV-positive donations from Minas Gerais, Brazil throughout 12 years and emphasize the importance of having a high rate of repeat donors in blood centers to reduce the residual risk of transfusion-transmitted infections., (© 2022 Wiley Periodicals LLC.)

Background: The inflammatory response plays a significant role in the outcome of coronavirus disease (COVID-19)., Methods: We investigated plasma cytokine and chemokine concentrations in non-infected (NI), asymptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected blood donors (AS), and patients with severe COVID-19 (SC)., Results: The SC group showed significantly higher levels of interleukin 6 (IL-6), IL-10, and CCL5 than the AS and NI groups. The SC and AS groups had considerably greater CXCL9 and CXCL10 concentrations than the NI group. Only NI and infected people showed separate clusters in the principal component analysis., Conclusions: SC, as well as AS was characterized by an inflammatory profile.

One of the effects of the pandemic in the hemotherapy services was the reduction in the attendance of blood donors and production of blood components. It is relevant to investigate how the capacity to meet the demand for blood components was affected, especially in blood centers located in the regions most affected by the pandemic, such as Brazil. This study aimed to describe the impact of the pandemic on the capacity to meet the demand for different types of blood components by a Brazilian blood center in 2020, compared to the historical series of 2016-2019 and to discuss the measures adopted to mitigate the effects of the pandemic. Retrospective cross-sectional study was carried out with comparative analysis of the blood components requested and attended in the period from 2016 to 2020. Data analysis was performed by Graphpad Prism 5. The spread of COVID-19 cases since March 2020 had impact on the blood components production and transfusions. The reduction in the production of blood components was observed prior to the restriction measures, in March 2020. In comparison to 2016-2019, there was a reduction in the number of transfusions performed in all months of 2020. The results suggest that the measures adopted in a Brazilian blood center to face the COVID-19 pandemic resulted in reasonable regularity in the supply of blood components. The sharing of experiences between blood banks in different regions, social and epidemiological contexts can contribute to the improvement of strategies to reduce the impact of COVID-19 in transfusion medicine., Competing Interests: Declaration of Competing Interest The authors have disclosed no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country., Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning., Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53)., Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread., Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem., Competing Interests: CP, LB, CW, TS, MO, RP, IM, LD, MB, NT, RF, VB, FM, AM, Cd, NS, SF, KF, Ld, LS, PI, LX, MC, NF, FA, LC, VP, MR, Rd, Sd, AC, MV, Md, EL, LF, SM, GN, AS, MB, MC, CD, OR, NF, VN, ES No competing interests declared, (© 2022, Prete, Buss, Whittaker et al.)

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear Cu II coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with N-pyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu 3 (C 18 H 16 N 5 O 2 ) 2 (C 18 H 17 N 5 O 2 ) 2 (H 2 O)]4BF 4 ∙H 2 O (1), and [Cu 3 (C 18 H 16 N 5 O 2 ) 2 (C 18 H 17 N 5 O 2 ) 2 (H 2 O) 3 ]4BF 4 ∙3H 2 O (%) (2) were synthesized using h2py and h3py with Cu(BF 4 ) 2 ∙nH 2 O as precursor, whereas the [Cu(C 18 H 17 N 5 O 2 )Cl 2 ]∙0.5H 2 O complex (3) was synthesized with h2py and CuCl 2 ∙2H 2 O. Crystallographic studies of complex 1, showed that coordination of hydrazones to Cu II occurs by tridentate modes of type κ 3 (O,N,N') as well as bidentate modes of type κ 2 (O',N″). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI 50 values. Complexes 1 and 2 were more active than complex 3, suggesting an effect of the complex charge on their activities. The interactions of such complexes towards bovine serum albumin (BSA) and DNA plasmid (pGEX-4 T1) were investigated using fluorescence spectroscopy and gel electrophoresis. All complexes were shown to interact with the DNA model as metallonucleases, but no interaction with BSA was observed. DNA molecular docking of complex 1 encompassing both its trinuclear (TN) form and a possible mononuclear (MN) derivative suggests that naphthyridyl ring performs π-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders., (Copyright © 2022. Published by Elsevier Inc.)

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.

We report a synthetic strategy that allows for the preparation of sterically encumbered heteroleptic Ru(II)porphyrinates with the desired configuration of stable/inert and weak/labile axial ligands to direct reactions between substrates to exclusively occur at the sterically encumbered face. To demonstrate the method, we describe the synthesis of a strapped-Ru(II)porphyrinate bearing a stable/inert triphenylphosphine (PPh 3 ) bulky axial ligand coordinated exo to the central cavity and a weak/labile methanol molecule coordinated at the internal axial position. With this axial ligand configuration, the reported Ru(II)porphyrinate exclusively promotes carbene transfer reactions to olefins through the central cavity, which has been verified by the selective formation of cycloprane-linked [2]rotaxanes.

In the present work, we developed and evaluated the performance of a new flow cytometry-based single platform, referred to as "FC-Duplex IgG1 (HTLV-1/2)", for universal and differential serodiagnosis of HTLV-1/2 infection. The proposed technology employs a system for detection of IgG1 antibodies in a single competitive immunofluorescence platform by flow cytometry using fluorescently labeled MT-2/MoT cell line mix coupled to a highly sensitive development system (Biotin/Streptavidin/Phycoerythrin). The stability of fluorescent labeling and the antigenicity of MT-2 and MoT cell lines were confirmed upon storage at -20°C for 2, 6, and 12 months. The anti-HTLV-1/2 IgG1 reactivity, expressed as percentage of positive fluorescent cells (PPFC), was evaluated for each target antigen along the titration curve of test serum samples (1:32 to 1:4,096). Upon selection of target cell line and serum dilutions with higher segregation score between groups, the performance of "FIX" and "FIX & PERM" protocols was evaluated. The "FIX" protocol presented excellent performance indices (Se = 92%/Sp = 94%/AUC = 0.96; Se = 96%/Sp = 100%/AUC = 0.99) for the universal (HTLV-1/2 vs. NI) and differential (HTLV-1 vs. HTLV-2) diagnosis of HTLV-1 infection, respectively. Optimization of the "FIX" protocol using the principle of synchronous and asynchronous pairwise analysis further improved the performance of "FC-Duplex IgG1 (HTLV-1/2)", using the "FIX" protocol for differential diagnosis of HTLV-1 and HTLV-2 infections (Se = 100%/Sp = 100%/AUC = 1.00). In conclusion, the "FC-Duplex IgG1 (HTLV-1/2)" method represents an innovation in the biotechnology segment with the potential to compose a serological kit for differential diagnosis of HTLV-1/2 infection for reference laboratories and blood centers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pimenta de Paiva, Coelho-dos-Reis, Trindade, Peruhype-Magalhães, Silva Araújo, Gonçalves, Nogueira, Pereira Martins, Lopes Ribeiro, Starling, Alcântara, Ribeiro, Carneiro-Proietti, Sabino, Alves Bicalho, Teixeira-Carvalho and Martins-Filho.)

During epidemics, data from different sources can provide information on varying aspects of the epidemic process. Serology-based epidemiologic surveys could be used to compose a consistent epidemic scenario. We assessed the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in serum samples collected from 7,837 blood donors in 7 cities of Brazil during March-December 2020. Based on our results, we propose a modification in a compartmental model that uses reported number of SARS-CoV-2 cases and serology results from blood donors as inputs and delivers estimates of hidden variables, such as daily values of SARS-CoV-2 transmission rates and cumulative incidence rate of reported and unreported SARS-CoV-2 cases. We concluded that the information about cumulative incidence of a disease in a city's population can be obtained by testing serum samples collected from blood donors. Our proposed method also can be extended to surveillance of other infectious diseases.

It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country. A previous REDS study using the same database from 2007 to 2009 showed that the prevalence per 100,000 donors was 222 in Recife, 83 in Belo Horizonte and 101 in São Paulo. From 2007 to 2016, HTLV-1/2 prevalence was calculated by year, blood center and birth cohort. Covariates included age, gender, schooling, self-reported skin color and type of donation. From 1,092,174 first-blood donations, in the general analysis, HTLV-1/2 infection predominated in females, donors over 50 years of age, black skin color and less educated. The average prevalence was 228 per 100,000 donors in Recife, 222 in Rio de Janeiro, 104 in Belo Horizonte and 103 in São Paulo. In the 10-year analysis, HTLV-1/2 prevalence was stable, but a trend was observed toward an increase in HTLV-1/2 infection among younger people ( p < 0.001), males ( p = 0.049), those with white skin color ( p < 0.001), and higher education ( p = 0.014). Therefore, this 10-year surveillance of the infection showed stable HTLV-1/2 prevalence overall but a trend toward increased prevalence among the younger and more educated donors despite Brazilian policies to control sexually transmitted infections being in place for more than 10 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miranda, Utsch-Gonçalves, Piassi, Loureiro, Gomes, Ribeiro, de Almeida-Neto, Blatyta, Amorim, Garcia Mateos, Murphy, Custer, Carneiro-Proietti and Sabino.)

The monoaminergic theory of depression/anxiety disorders cannot fully explain the behavioral and neuroplastic changes observed after ADs chronic treatment. Endocannabinoid system, which comprises CB2 receptors, has been associated with the chronic effects of these drugs, especially in stressed mice. CB2-KO mice display more vulnerability to stressful stimuli. In the present study, we hypothesized that the behavioral and neuroplastic effects observed after repeated treatment with the AD escitalopram (Esc) in chronically stressed mice depend on CB2 receptor signaling. Male mice submitted to chronic unpredictable stress (CUS) paradigm (21 days) were treated daily with AM630 (0.01; 0.03 or 0.3 mg/kg, i.p) a CB2 receptor antagonist/inverse agonist. At e 19th day of the CUS protocol, mice were submitted to Open field test and Tail-suspension test to evaluate antidepressant-like behavior. At the end of the stress protocol, mice were submitted to Novel Suppressed Feeding test (day 22nd) to evaluate anxiety-like behavior. In a second series of experiments, male mice treated with Esc (10 mg/kg, daily, 21 days) in the presence or not of AM630 (0.30 mg/kg) were submitted to the same round of behavioral tests in the same conditions as performed in the dose-response curve protocol. Animals were then euthanized under deep anesthesia, and their brains/hippocampi removed for immunohistochemistry (Doublecortin-DCX) or Western Blot assay. Our results demonstrated that chronic treatment with AM630, a CB2 antagonist/inverse agonist, induces anxiolytic-like effects in stressed mice. Moreover, chronic reduction of CB2 receptor endogenous activity by AM630 attenuated the neuroplastic (potentiating stress-induced decreased expression of pro-BDNF, but enhanced pmTOR and DAGL expression in the hippocampus reduced in stressed mice), the antidepressant- but not the anxiolytic-like effects of Esc. AM630 alone or in combination with Esc decreased the expression of DCX + cell in both the subgranular and granular layers of the dentate gyrus (DG), indicating a general reduction of DCX + neuroblasts and a decrease in their migration through the DG layers. We suggest that the antidepressant-like behavior and the pro-neurogenic effect, but not the anxiolytic like behavior, promoted by Esc in stressed mice are, at least in part, mediated by CB2 receptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ribeiro, Aguiar, Scarante, Fusse, de Oliveira, Guimaraes and Campos.)

A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the N -terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.

Introduction: Bronchiectasis patients may present a reduced functional capacity due to an increase in the ventilatory demand during exercise., Objective: To evaluate the effects of controlled voluntary hyperinflation and increased respiratory rate on the mechanics of the respiratory system, simulating what happens during exercise, in bronchiectasis and healthy subjects., Methods: Bronchiectasis (n=30) and healthy (n=16) subjects were evaluated by impulse oscillometry (IOS) during a baseline condition, and in controlled conditions with baseline (b) tidal volume (V) and hyperinflation (H), with respiratory rates at 30(R30) and 40(R40) bpm, in a random order. The mixed effects and a significance level at 0.05 were used for comparisons., Results: Resistance at 5Hz (R5), and at minus 20Hz (R5-R20), in kPa/L/s, were higher in subjects with bronchiectasis in all experimental conditions (p<0.05). For the bronchiectasis group, R5 and R5-20 increased with R increase at V (VRb versus VR30 and VR40; VR30 versus VR40; R5, R20 and R5-20 increased with R increase at H (HRb versus HR40; HR30 versus HR40). For the same R, there was a decrease with H compared to V (HRb versus VR30 and VR40; and HR30 versus VR30 and VR40). For the healthy group, only R20 showed differences (HR30 versus HR40; HR40 versus VR40)., Conclusion: The tachypnea increases the resistance and reactance of the respiratory system in bronchiectasis patients, and the voluntary hyperinflation caused attenuates this increase. These results can guide the development of strategies to reduce the limitation of physical activity in patients with bronchiectasis., (Copyright © 2020 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Phospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A 2 (PLA 2 ) is a phospholipid metabolizing enzyme that releases free fatty acids, mostly arachidonic acid, and lysophospholipids, which contribute to the development of the tumor microenvironment (TME), promoting immune evasion, angiogenesis, tumor growth, and invasiveness. The mechanisms mediated by PLA 2 are not fully understood, especially because an important inhibitory molecule, Annexin A1, is present in the TME but does not exert its action. Here, we will discuss how Annexin A1 in cancer does not inhibit PLA 2 leading to both pro-inflammatory and pro-tumoral signaling pathways. Moreover, Annexin A1 promotes the release of cancer-derived exosomes, which also lead to the enrichment of PLA 2 and COX-1 and COX-2 enzymes, contributing to TME formation. In this review, we aim to describe the role of PLA 2 in the establishment of TME, focusing on cancer-derived exosomes, and modulatory activities of Annexin A1. Unraveling how these proteins interact in the cancer context can reveal new strategies for the treatment of different tumors. We will also describe the possible strategies to inhibit PLA 2 and the approaches that could be used in order to resume the anti-PLA 2 function of Annexin A1.

Background: Fruit by-products contain phytochemicals, fibers and other components that can improve the redox imbalance of obesity., Objective: The objective was to evaluate the effects of consumption of by-products of acerola, cashew and guava on the adiposity and redox homeostasis of adipose tissue in obese rats., Methods: The animals were separated into 5 groups, control (CTL), high fat (HF), HF supplemented with acerola (HFA), cashew (HFC) and guava (HFG)., Results: Thiol quantification, lipid profile, catalase (CAT) and glutathione peroxidase (GPX) test were performed. TGL and VLDL levels were increased in HF group, and the treated groups did not change the lipid profile. CAT activity was increased in HFA and HFG groups. HFA was able to reduce the weight of the subcutaneous cushion., Conclusion: Treatment with fruit by-products did not alter weight gain, energy efficiency and body weight. Thus, the by-products of acerola and guava can be used as a sustainable alternative in the treatment of obesity., Competing Interests: Declaration of competing interest No potential conflict of interest is reported by the authors., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: One of the effects of the coronavirus disease 2019 (COVID-19) pandemic is the risk of shortages in Blood Centres., Objectives: To verify the impact of the COVID-19 pandemic on the blood donor's attendance and production of blood components in Fundação Hemominas, a Brazilian public institution was formed by several Blood Centres., Methods: A cross-sectional study was carried out from January to June 2020. Data collected were compared to a historical series from 2016 to 2019., Results: The study showed a reduction in the attendance of blood donors, whole blood collections and blood component production from March 2020, when the first case of COVID-19 was notified in Minas Gerais, Brazil. The results evidenced that Hemominas Blood Centres were affected in a very distinct way by the pandemic with a general mean reduction around 17% in attendance of blood donors and in production of blood components in the period of March to June. On the other hand, the return of blood donors rate increased., Conclusion: The reduction in blood donation during the pandemic period was significant, despite the measures adopted. Still, the recruitment of return donors appears to be an important measure to be considered to decrease the pandemic's effect on blood stocks., (© 2020 British Blood Transfusion Society.)

Background: Cavernous hemangiomas are congenital hamartomatous lesions that originate from mesodermal tissue composed of dilated blood vessels. Abdominal pain and palpable mass are the most common presenting symptoms. The different types of treatment for symptomatic patients remain controversial. However, surgical resection is always the most preferred method when possible. To date, there are no reports of endoscopic ultrasound-guided (EUS-guided) absolute ethanol injection as a treatment for such disease when surgery is not an option., Case Presentation: A 19-year-old girl with giant cavernous intra-abdominal hemangioma extending to the hepatic hilum, also affecting the gastric wall and occupying the entire supra-mesocolic cavity, initially presents with upper gastrointestinal bleeding and loss of 20 kg in 1 year (BMI = 18 kg/m 2 ). Percutaneous angiography identified a mass with arterial blood supply by the left gastric artery that was embolized. After re-bleeding, an alternative treatment with EUS-guided injection of alcohol was proposed once resection was not feasible without major risks to a young patient. This procedure was repeated 15 and 45 days after the initial treatment, with the ethanol injection of 25 cc and 15 cc, respectively. On the second and third procedure dates, there was evident regression of the hemangioma. On the third procedure, it was possible to identify all anatomic structures that were not clear on the first EUS. After 45 days of last injection, abdominal CT and EUS showed notorious regression of the lesion. Eight months later, abdominal CT showed only a remnant lesion in the hepatogastric ligament with 129 cm 3 on volumetry (87% lower in comparison to the initial image), and the patient remains asymptomatic with BMI of 26. In the most recent follow-up CT, 4 years and 2 months after first treatment, the patient presents with a slight increase in the hemangioma-now with 183 cm 3 on volumetry., Conclusion: Transgastric EUS-guided ethanol injection in the treatment of giant intra-abdominal cavernous hemangioma can provide good outcomes without major complications and can be repeated if necessary.

Importance: Intensity and duration of the COVID-19 pandemic, and planning required to balance concerns of saving lives and avoiding economic collapse, could depend significantly on whether SARS-CoV-2 transmission is sensitive to seasonal changes., Objective: Hypothesis is that increasing temperature results in reduced SARS CoV-2 transmission and may help slow the increase of cases over time., Setting: Fifty representative Northern Hemisphere countries meeting specific criteria had sufficient COVID-19 case and meteorological data for analysis., Methods: Regression was used to find the relationship between the log of number of COVID-19 cases and temperature over time in 50 representative countries. To summarize the day-day variability, and reduce dimensionality, we selected a robust measure, Coefficient of Time (CT), for each location. The resulting regression coefficients were then used in a multivariable regression against meteorological, country-level and demographic covariates., Results: Median minimum daily temperature showed the strongest correlation with the reciprocal of CT (which can be considered as a rate associated with doubling time) for confirmed cases (adjusted R2 = 0.610, p = 1.45E-06). A similar correlation was found using median daily dewpoint, which was highly colinear with temperature, and therefore was not used in the analysis. The correlation between minimum median temperature and the rate of increase of the log of confirmed cases was 47% and 45% greater than for cases of death and recovered cases of COVID-19, respectively. This suggests the primary influence of temperature is on SARS-CoV-2 transmission more than COVID-19 morbidity. Based on the correlation between temperature and the rate of increase in COVID-19, it can be estimated that, between the range of 30 to 100 degrees Fahrenheit, a one degree increase is associated with a 1% decrease-and a one degree decrease could be associated with a 3.7% increase-in the rate of increase of the log of daily confirmed cases. This model of the effect of decreasing temperatures can only be verified over time as the pandemic proceeds through colder months., Conclusions: The results suggest that boreal summer months are associated with slower rates of COVID-19 transmission, consistent with the behavior of a seasonal respiratory virus. Knowledge of COVID-19 seasonality could prove useful in local planning for phased reductions social interventions and help to prepare for the timing of possible pandemic resurgence during cooler months., Competing Interests: The authors of the study have read the journal’s policy, and have the following competing interests to declare: MAAR is an employee of Pupa but contributed to this work independently of this affiliation. AK is currently employed by MyMD Pharmaceuticals; however, this affiliation was not held at the time this study was conducted. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. The authors have declared that no other competing interests exist.

Cannabidiol (CBD) is a phytocannabinoid with a broad-range of therapeutic potential in several conditions, including neurological (epilepsy, neurodegenerative diseases, traumatic and ischemic brain injuries) and psychiatric disorders (schizophrenia, addiction, major depressive disorder, and anxiety). The pharmacological mechanisms responsible for these effects are still unclear, and more than 60 potential molecular targets have been described. Regarding neuropsychiatric disorders, most studies investigating these mechanisms have focused on neuronal cells. However, glial cells (astrocytes, oligodendrocytes, microglia) also play a crucial role in keeping the homeostasis of the central nervous system. Changes in glial functions have been associated with neuropathological conditions, including those for which CBD is proposed to be useful. Mostly in vitro studies have indicated that CBD modulate the activation of proinflammatory pathways, energy metabolism, calcium homeostasis, and the proliferative rate of glial cells. Likewise, some of the molecular targets proposed for CBD actions are f expressed in glial cells, including pharmacological receptors such as CB1, CB2, PPAR-γ, and 5-HT1A. In the present review, we discuss the currently available evidence suggesting that part of the CBD effects are mediated by interference with glial cell function. We also propose additional studies that need to be performed to unveil the contribution of glial cells to CBD effects in neuropsychiatric disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scarante, Ribeiro, Almeida-Santos, Guimarães and Campos.)

This study describes the experimental design and optimization of application TiO 2 catalysts doped with 0.5, 1, 1.5, 2.0% of Fe. The catalysts were prepared using the impregnation method applied in Paraquat herbicide degradation. The catalysts were characterized by the following techniques: specific surface area and volume, mean pore diameter (BET method), scanning electron microscopy and photoacoustic spectroscopy. The characterization presented results indicating that both calcination temperature and the increase nominal metallic load affected by the structure of catalysts, changing the textural properties, as well as the band gap. The catalyst that presented the best herbicide removal percentage was TiO 2 calcined at 773 K with removal of 90.2%. However, according to the experimental design and optimization, both variables (calcination temperature and Fe percentage) are significant in the process. In addition, a positive effect was found in the interaction between the two variables. The values show that a third order kinetic model better described the Paraquat photocatalytic degradation.