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Aims: To estimate the prevalence of symptoms of temporomandibular disorders (TMD) as a function of age and gender, in a representative urban sample from the Brazilian population. Methods: A total of 1,230 inhabitants (51.5% women) aged 15 to 65 years were interviewed by a validated phone survey. Sample size had been previously calculated. TMD symptoms were assessed through five questions, as recommended by the American Academy of Orofacial Pain, in an attempt to identify possible TMD. Data were derived by age and gender. Prevalence of each TMD symptom, and of combination of symptoms, was calculated. Results: At least one TMD symptom was reported by 39.2% of the individuals. Pain related to TMD was noted by 25.6% of the population. Temporomandibular joint (TMJ) sound was the most common symptom of TMD, followed by TMJ pain and masticatory muscle pain. All symptoms were more prevalent in women than in men. With men used as the reference, a relative risk (RR) of at least one TMD symptom in women was 1.31 (95% confidence interval [CI] = 1.14 to 1.52). When at least two symptoms were present, the RR was 1.93 (95% CI = 1.49 to 2.51). For three or more TMD symptoms, the RR was 2.49 (95% CI = 1.67 to 3.71). Women were also more likely than men to have TMD pain (RR = 1.78; 9% CI = 1.45 to 2.18). Conclusion: Individual symptoms, as well as a combination of TMD symptoms, are prevalent in the Brazilian urban population and are more frequent in women than in men. Additional studies should focus on risk factors for and relevance of TMD for the sufferers. J Orofac Pain 2010;24:270-278. [ABSTRACT FROM AUTHOR]

The paper reviews the performance measurement in the domain of interest. Important data in asset management are further, discussed. The importance and the characteristics of today’s ICTs capabilities are also mentioned in the paper. The role of new concepts such as big data and data mining analytical technologies in managing the performance measurements in asset management are discussed in detail. The authors consequently suggest the use of the modified Balanced Scorecard methodology highlighting both quantitative and qualitative aspects, which is crucial for optimal use of the big data approach and technologies.

OBJETIVO: Avaliar a susceptibilidade a inseticidas químicos de larvas de Culex quinquefasciatus e Aedes aegypti, provenientes de áreas sujeitas ou não a tratamentos de controle. MÉTODOS: Foram coletadas larvas de mosquitos em uma área não sujeita a tratamentos com inseticidas (Campinas, SP) e em áreas sujeitas a esses tratamentos (Campo Grande, MS e Cuiabá, MT). Foram usados bioensaios com concentrações diagnóstico e concentrações múltipla de inseticidas organofosforados e piretróides, segundo padrão da Organização Mundial de Saúde, para avaliar a susceptibilidade dessas larvas. RESULTADOS: Ensaios com larvas de Culex quinquefasciatus de Campinas, SP, permitiram a suspeita de resistência à cipermetrina e evidenciaram resistência à ciflutrina. Larvas dessa espécie coletadas em Campo Grande, MS, e Campinas, SP, apresentaram resistência ao temephos. Para a colônia campineira desta espécie, foram estabelecidas as razões de resistência: RR50=6,36 e RR95=4,94, com base em linhagem susceptível padrão. Adicionalmente, os testes com Aedes aegypti mostraram susceptibilidade similar ao temephos em uma população de campo (Cuiabá, MT) e uma de laboratório. CONCLUSÕES: Os resultados indicam resistência a organofosforado e piretróides em Culex quinquefasciatus, evidenciando a necessidade de avaliações e monitoramento da efetividade dos inseticidas a serem usados nos programas de controle de mosquitos.

Populações de Simulium (Chirostilbia) pertinax Kollar, 1832 do Sul e Sudeste do Brasil, foram analisadas quanto à susceptibilidade ao Temephos, considerando-se os históricos de controle e possível resistência. Bioensaios in situ foram realizados para populações dos estados do Paraná (Tibaji e Rolândia), Rio de Janeiro (Muriqui) e São Paulo (Barra do Una, Ilhabela, e Morungaba). As populações foram caracterizadas como susceptíveis (S) ou resistentes (R) submetendo-se larvas nos últimos estádios a uma concentração operacional (0,1ppm i.a./10min) de Temephos (Abate 500E) como diagnóstica. Os possíveis mecanismos para o desenvolvimento de resistência ao organofosforado são discutidos considerando-se antigas e novas estratégias de controle.

OBJETIVO: A susceptibilidade dos insetos tem sido um dos mais importantes aspectos a ser monitorados em programas de saúde pública que tratam do controle de vetores. O estudo objetiva avaliar a susceptibilidade de larvas de Aedes aegypti a inseticidas químicos em áreas sujeitas ou não a controle. MÉTODOS: Bioensaios foram realizados com concentração de diagnóstico e concentração múltipla, segundo padrão da Organização Mundial de Saúde para as coletas de larvas de Aedes aegypti, em uma área não sujeita -- Campinas, SP -- e em uma outra área sujeita -- Campo Grande, MS -- a tratamentos químicos de controle. RESULTADOS: Larvas de Aedes aegypti coletadas em Campinas indicaram resistência potencial à concentração-diagnóstico (CD) de 0,04 ppm do organofosforado temephos. O teste de concentração múltipla registrou sobrevivência de 24,5% à concentração de 0,0125 ppm. A susceptibilidade dessa mesma linhagem foi avaliada para o organofosforado fenitrothion (CD=0,08 ppm) e o piretróide cipermetrina (CD=0,01 ppm), resultando em valores normais para essas concentrações. Larvas de Ae. aegypti coletadas em Campo Grande mostraram susceptibilidade normal ao temephos (CD=0,04 ppm) e à cipermetrina (CD=0,01 ppm). Também foram estabelecidas as CL50 e as CL95 de cipermetrina 25 CE, cyfluthrin 5 CE, betacyfluthrin 1,25 SC e propoxur 20 CE para Ae. aegypti. Com base nos dados da linhagem-padrão Rockefeller, foram estimadas as razões de resistência de 2,9, 2,2, 2,4 e 1,3, respectivamente, pela CL50, e de 3,5, 2,6, 3,9 e 1,3 pela CL95. CONCLUSÃO: Os resultados reforçam a necessidade de avaliações prévias e monitoramento da efetividade dos inseticidas que devem ser usados em programas de controle de mosquitos.

Abstract Background Recent findings indicate that several insect lineages receive protection against particular natural enemies through infection with heritable symbionts, but little is yet known about whether enemies are able to discriminate and respond to symbiont-based defense. The pea aphid, Acyrthosiphon pisum, receives protection against the parasitic wasp, Aphidius ervi, when infected with the bacterial symbiont Hamiltonella defensa and its associated bacteriophage APSE (Acyrthosiphon pisum secondary endosymbiont). Internally developing parasitoid wasps, such as A. ervi, use maternal and embryonic factors to create an environment suitable for developing wasps. If more than one parasitoid egg is deposited into a single aphid host (superparasitism), then additional complements of these factors may contribute to the successful development of the single parasitoid that emerges. Results We performed experiments to determine if superparasitism is a tactic allowing wasps to overcome symbiont-mediated defense. We found that the deposition of two eggs into symbiont-protected aphids significantly increased rates of successful parasitism relative to singly parasitized aphids. We then conducted behavioral assays to determine whether A. ervi selectively superparasitizes H. defensa-infected aphids. In choice tests, we found that A. ervi tends to deposit a single egg in uninfected aphids, but two or more eggs in H. defensa-infected aphids, indicating that oviposition choices may be largely determined by infection status. Finally, we identified differences in the quantity of the trans-β-farnesene, the major component of aphid alarm pheromone, between H. defensa-infected and uninfected aphids, which may form the basis for discrimination. Conclusions Here we show that the parasitic wasp A. ervi discriminates among symbiont-infected and uninfected aphids, and changes its oviposition behavior in a way that increases the likelihood of overcoming symbiont-based defense. More generally, our results indicate that natural enemies are not passive victims of defensive symbionts, and that an evolutionary arms race between A. pisum and the parasitoid A. ervi may be mediated by a bacterial symbiosis.

Offering secure and anonymous communications in mobile ad hoc networking environments is essential to achieve confidence and privacy, thus promoting widespread adoption of this kind of networks. In addition, some minimum performance levels must be achieved for any solution to be practical and become widely adopted. In this paper, we propose and implement HOP, a novel solution based on cryptographic Host Identity Protocol (HIP) that offers security and user-level anonymity in MANET environments while maintaining good performance levels. In particular, we introduce enhancements to the authentication process to achieve Host Identity Tag (HIT) relationship anonymity, along with source/destination HIT anonymity when combined with multihoming. Afterward we detail how we integrate our improved version of HIP with the OLSR routing protocol to achieve efficient support for pseudonyms. We implemented our proposal in an experimental testbed, and the results obtained show that performance levels achieved are quite good, and that the integration with OLSR is achieved with a low overhead.

Generoso Guerra Bautista,1 Ricardo Machado Xavier,2 Maria de la Vega,3 J Abraham Simón-Campos,4 Gastón Solano,5 Ronald D Pedersen,6 Bonnie Vlahos,6 Cecilia Borlenghi7 1Centro de Investigación Marbella, Paitilla Panamá, Panamá; 2Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 3CEIM Investigaciones Medicas, Buenos Aires, Argentina; 4Köhler & Milstein Research, Mérida, México; 5Pfizer, San José, Costa Rica; 6Pfizer, Collegeville, PA, USA; 7Pfizer, Buenos Aires, ArgentinaCorrespondence: Generoso Guerra BautistaConsultorios Royal Center, Calle 53 Marbella, Panamá, República de PanamáTel +507-263-3283Email generosoguerra@icloud.comBackground: In rheumatoid arthritis (RA), little is known about clinical responses to treatment as predictors of patient-reported outcome (PRO) changes. In this post hoc analysis, we examined the relationship between clinical outcomes at week 12 and PRO changes at week 24 in patients with RA.Methods: In an open-label study, Latin American patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX) were randomized to receive etanercept 50 mg/week plus MTX (ETN+MTX; n=281) or an additional conventional disease-modifying anti-rheumatic drug (DMARD) plus MTX (DMARD+MTX; n=142) for 24 weeks. The PROs included Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form (SF-36), Physician and Patient Global Assessment scores (PGA, PtGA), Physician and Patient Satisfaction, and an activity impairment assessment. PRO changes at week 24 were calculated by week-12 improvements using the American College of Rheumatology criteria (ACR

Real-world evidence on the impact of monoclonal antibodies as first-line treatment in Spain is limited. This observational, retrospective and prospective, multicenter, descriptive study included 117 transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients divided into Group A, who received no daratumumab standard regimens, and the DVMP group (daratumumab, bortezomib, melphalan, and prednisone treatment). More than 90% of the patients in Group A received bortezomib, lenalidomide, or a combination of them. The median follow-up time for Group A was 38.2 months in comparison to 25.8 months for the DVMP group ( p < 0.0001). The rate of DVMP patients that experienced disease progression or death from any cause was 36.8%, compared to 67.3% of Group A patients at 36 months of follow-up. The DVMP group had a higher 36-month progression-free survival (PFS) rate (52.9% vs. 31.7%). During the retrospective period, 73.0% of patients reported adverse drug reactions, while in the prospective period, 40.5% experienced adverse events, with no clinical differences between groups. The study supports the use of daratumumab regimens in frontline therapy based on real-world data. The findings provide valuable insights into the clinical outcomes of daratumumab therapy, which can help physicians make informed decisions regarding the optimal treatment approach for this patient population.

Background: Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established., Methods: In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days. Patients who were fully vaccinated against Covid-19 and who had at least one risk factor for severe disease, as well as patients without such risk factors who had never been vaccinated against Covid-19 or had not been vaccinated within the previous year, were eligible for participation. Participants logged the presence and severity of prespecified Covid-19 signs and symptoms daily from day 1 through day 28. The primary end point was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Covid-19-related hospitalization and death from any cause were also assessed through day 28., Results: Among the 1296 participants who underwent randomization and were included in the full analysis population, 1288 received at least one dose of nirmatrelvir-ritonavir (654 participants) or placebo (634 participants) and had at least one postbaseline visit. The median time to sustained alleviation of all targeted signs and symptoms of Covid-19 was 12 days in the nirmatrelvir-ritonavir group and 13 days in the placebo group (P = 0.60). Five participants (0.8%) in the nirmatrelvir-ritonavir group and 10 (1.6%) in the placebo group were hospitalized for Covid-19 or died from any cause (difference, -0.8 percentage points; 95% confidence interval, -2.0 to 0.4). The percentages of participants with adverse events were similar in the two groups (25.8% with nirmatrelvir-ritonavir and 24.1% with placebo). In the nirmatrelvir-ritonavir group, the most commonly reported treatment-related adverse events were dysgeusia (in 5.8% of the participants) and diarrhea (in 2.1%)., Conclusions: The time to sustained alleviation of all signs and symptoms of Covid-19 did not differ significantly between participants who received nirmatrelvir-ritonavir and those who received placebo. (Supported by Pfizer; EPIC-SR ClinicalTrials.gov number, NCT05011513.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination., Methods: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30 μg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed., Results: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported., Conclusions: Among 5- to  < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified., (© 2024. Pfizer Inc.)

The comprehension and modeling of the mechanical behavior of soft biological tissues are essential due to their clinical applications. This knowledge is essential for predicting tissue responses accurately and enhancing our ability to compute the behavior of biological structures and bio-prosthetic devices under specific loading conditions. The current research is centered on modeling the initiation and progression of soft tissues damage, which typically exhibit intricate anisotropic and nonlinear elastic characteristics. For this purpose, the following study presents a comparative analysis of the computational performance of two distinct damage modeling techniques. The first technique employs a well-established damage model, based on a piece-wise exponential damage function as proposed by Calvo et al. (Int J Numer Methods Eng 69:2036-2057, 2007. https://doi.org/10.1002/nme.1825 ). The second approach adopts a sigmoid function, as proposed by López-Campos et al. (Comput Methods Biomech Biomed Eng 23(6):213-223. https://doi.org/10.1080/10255842.2019.1710742 ). The aim of this study is to verify the validity of the López-Campos sigmoid-based damage model to be used in finite element simulation, the implementation of which is unknown. For this proposal, both models were implemented within a commercial Finite Element software package, and their responses to local and non-local damage algorithms were assessed in depth through two standard benchmark tests: a plate with a hole and a ball burst. The results of this study indicate that, for a wide range of cases, such as in-plane stresses, out-plane stresses, stress concentration and contact, all over large displacement conditions, the López-Campos damage model shows a good response to non-local algorithms achieving mesh independence and convergence in all these cases. The results obtained are in line with those obtained for the Calvo's damage model, showing, in addition, larger deformations under in-plane stress and stress concentration conditions and a lower number of iterations under out-plane stress and contact conditions. Consequently, the López-Campos' damage model emerges as a valuable and useful tool in the field of mechanical damage research in biological systems., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: In the phase 3 TACKLE study, outpatient treatment with AZD7442 (tixagevimab/cilgavimab) was well tolerated and significantly reduced progression to severe disease or death through day 29 in adults with mild-to-moderate coronavirus disease 2019 (COVID-19) at the primary analysis. Here, we report data from the final analysis of the TACKLE study, performed after approximately 15 months' follow-up., Methods: Eligible participants were randomized 1:1 and dosed within 7 days of symptom onset with 600 mg intramuscular AZD7442 (n = 456; 300 mg tixagevimab/300 mg cilgavimab) or placebo (n = 454)., Results: Severe COVID-19 or death through day 29 occurred in 4.4% and 8.8% of participants who received AZD7442 or placebo, a relative risk reduction (RRR) of 50.4% [95% confidence interval (CI) 14.4, 71.3; p = 0.0096]; among participants dosed within 5 days of symptom onset, the RRR was 66.9% (95% CI 31.1, 84.1; p = 0.002). Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 occurred in 5.0% of participants receiving AZD7442 versus 9.7% receiving placebo, an RRR of 49.2% (95% CI 14.7, 69.8; p = 0.009). Adverse events occurred in 55.5% and 55.9% of participants who received AZD7442 or placebo, respectively, and were mostly mild or moderate in severity. Serious adverse events occurred in 10.2% and 14.4% of participants who received AZD7442 or placebo, respectively, and deaths occurred in 1.8% of participants in both groups. Serum concentration-time profiles recorded over 457 days were similar for AZD7442, tixagevimab, and cilgavimab, and were consistent with the extended half-life reported for AZD7442 (approx. 90 days)., Conclusions: AZD7442 reduced the risk of progression to severe COVID-19, hospitalization, and death, was well tolerated through 15 months, and exhibited predictable pharmacokinetics in outpatients with mild-to-moderate COVID-19. These data support the long-term safety of using long-acting monoclonal antibodies to treat COVID-19., Trial Registration: Clinicaltrials.gov, NCT04723394. ( https://clinicaltrials.gov/study/NCT04723394 ., (© 2024. The Author(s).)

Introduction: We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study., Methods: Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset., Results: Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1-2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively., Conclusions: AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19., Clinical Trial Registration: Clinicaltrials.gov, NCT04723394. ( https://beta., Clinicaltrials: gov/study/NCT04723394 )., (© 2023. The Author(s).)

Environmental vulnerability is an important tool to understand the natural and anthropogenic impacts associated with the susceptibility to environmental damage. This study aims to assess the environmental vulnerability of the Doce River basin in Brazil through Multicriteria Decision Analysis based on Geographic Information Systems (GIS-MCDA). Natural factors (slope, elevation, relief dissection, rainfall, pedology, and geology) and anthropogenic factors (distance from urban centers, roads, mining dams, and land use) were used to determine the environmental vulnerability index (EVI). The EVI was classified into five classes, identifying associated land uses. Vulnerability was verified in water resource management units (UGRHs) and municipalities using hot spot analysis. The study employed the water quality index (WQI) to assess the EVI and global sensitivity analysis (GSA) to evaluate the model input parameters that most influence the basin's environmental vulnerability. The results showed that the regions near the middle Doce River were considered environmentally more vulnerable, especially the UGRHs Guandu, Manhuaçu, and Caratinga; and 35.9% of the basin has high and very high vulnerabilities. Hot spot analysis identified regions with low EVI values (cold spot) in the north and northwest, while areas with high values (hot spot) were concentrated mainly in the middle Doce region. Water monitoring stations with the worst WQI values were found in the most environmentally vulnerable areas. The GSA determined that land use and slope were the primary factors influencing the model's response. The results of this study provide valuable information for supporting environmental planning in the Doce River basin., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this pathway would be a novel approach to the treatment of patients with autoimmune or autoinflammatory diseases., Methods: In this phase 2a, double-blind, randomized, placebo-controlled trial, we assigned, in a 2:1:1 ratio, adult patients with moderate-to-severe rheumatoid arthritis who had had an inadequate response to, a loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or to biologic or targeted synthetic DMARDs to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks. The primary outcome was the change from baseline to week 12 in the Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP). The DAS28-CRP ranges from 0 to 9.4, with higher scores indicating more severe disease. The primary comparison was between the 700-mg group and the placebo group. Secondary outcomes included the percentages of patients with American College of Rheumatology 20 (ACR20), ACR50, and ACR70 responses - defined as improvements from baseline of 20%, 50%, and 70% or more, respectively, in the numbers of tender and swollen joints and in at least three of five important domains - at week 12., Results: At week 12, the change from baseline in the DAS28-CRP was significantly greater in the 700-mg peresolimab group than in the placebo group (least-squares mean change [±SE], -2.09±0.18 vs. -0.99±0.26; difference in change, -1.09 [95% confidence interval, -1.73 to -0.46]; P<0.001). The results of the analyses of secondary outcomes favored the 700-mg dose over placebo with respect to the ACR20 response but not with respect to the ACR50 and ACR70 responses. Adverse events were similar in the peresolimab and placebo groups., Conclusions: Peresolimab showed efficacy in a phase 2a trial in patients with rheumatoid arthritis. These results provide evidence that stimulation of the PD-1 receptor has potential efficacy in the treatment of rheumatoid arthritis. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT04634253.)., (Copyright © 2023 Massachusetts Medical Society.)

As the number of introduced species keeps increasing unabatedly, identifying and prioritising current and potential Invasive Alien Species (IAS) has become essential to manage them. Horizon Scanning (HS), defined as an exploration of potential threats, is considered a fundamental component of IAS management. By combining scientific knowledge on taxa with expert opinion, we identified the most relevant aquatic IAS in the Iberian Peninsula, i.e., those with the greatest geographic extent (or probability of introduction), severe ecological, economic and human health impacts, greatest difficulty and acceptability of management. We highlighted the 126 most relevant IAS already present in Iberian inland waters (i.e., Concern list) and 89 with a high probability of being introduced in the near future (i.e., Alert list), of which 24 and 10 IAS, respectively, were considered as a management priority after receiving the highest scores in the expert assessment (i.e., top-ranked IAS). In both lists, aquatic IAS belonging to the four thematic groups (plants, freshwater invertebrates, estuarine invertebrates, and vertebrates) were identified as having been introduced through various pathways from different regions of the world and classified according to their main functional feeding groups. Also, the latest update of the list of IAS of Union concern pursuant to Regulation (EU) No 1143/2014 includes only 12 top-ranked IAS identified for the Iberian Peninsula, while the national lists incorporate the vast majority of them. This fact underlines the great importance of taxa prioritisation exercises at biogeographical scales as a step prior to risk analyses and their inclusion in national lists. This HS provides a robust assessment and a cost-effective strategy for decision-makers and stakeholders to prioritise the use of limited resources for IAS prevention and management. Although applied at a transnational level in a European biodiversity hotspot, this approach is designed for potential application at any geographical or administrative scale, including the continental one., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile., (© 2023. The Author(s).)

Background: Appetite represents a desire of a person to eat specific food in order to reach satisfaction and pleasure states. This desire may be associated with the experience of negative or positive emotions (emotional appetite). Emotional appetite can influence eating behavior, and its investigation is relevant to avoid possible damage to health resulting from a disordered eating., Objectives: To adapt the Emotional Appetite Questionnaire (EMAQ) to the Portuguese language; to assess the validity and reliability of the data; and to assess emotional appetite in three samples of adults collected before and after the outbreak of the COVID-19 pandemic., Methods: This is a cross-sectional study with non-probabilistic convenience sampling. The Portuguese version of the EMAQ was presented after translation, back-translation, and content analysis. Two studies were conducted, the first before and the second after the pandemic onset. Three samples were formed (2019: Sample 1 (age = 19.7 ± 1.5 years) n = 323; 2020: Sample 2 (age = 21.3 ± 1.8 years) n = 1,011; and Sample 3 (age = 28.9 ± 3.1 years) n = 909). An exploratory strategy with parallel analysis was performed. The analyses were conducted in FACTOR and R (lavaan and semTools packages) software. After determining the best-fit model for the data, emotional appetite was examined considering decrease, non-alteration, and increase in appetite in the face of positive and negative emotions/situations. The profile of emotional appetite was determined using a circumplex model., Results: The two-factor model described by the valence of emotions/situations fitted the samples (Comparative Fit Index minimum-maximum = 0.95-0.98; Tucker-Lewis Index = 0.94-0.98; Root Mean Square Error of Approximation = 0.03-0.08; α ord = 0.78-0.88). Increases in appetite were more frequent for positive emotions/situations (52.0-57.5%), and both decreases (35.4-44.5%) and increases (50.0-56.2%) in appetite were observed for negative emotions/situations. Emotions with negative valence and activation were more relevant to appetite reduction, while a significant increase in appetite was observed with anxiety (negative valence and positive activation)., Conclusion: Different emotions and situations may influence appetite in people, and such an investigation may be useful in preparing eating protocols., Competing Interests: The authors declare that they have no competing interests., (© 2023 Martins et al.)

Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function. We report a recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families. The patients exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii , and presented with agammaglobulinemia. Patients' B cells showed impaired maturation, decreased immunoglobulin isotype switching, and defective plasma cell differentiation, whereas their T cells contained reduced T H 17 and T FH populations and exhibited decreased cytokine production. A knock-in mouse model of heterozygous T95R showed a severe defect in antibody production both at the steady state and after immunization with different types of antigens, consistent with the CID observed in these patients. The IRF4 T95R variant maps to the TF's DNA binding domain, alters its canonical DNA binding specificities, and results in a simultaneous multimorphic combination of loss, gain, and new functions for IRF4. IRF4 T95R behaved as a gain-of-function hypermorph by binding to DNA with higher affinity than IRF4 WT . Despite this increased affinity for DNA, the transcriptional activity on IRF4 canonical genes was reduced, showcasing a hypomorphic activity of IRF4 T95R . Simultaneously, IRF4 T95R functions as a neomorph by binding to noncanonical DNA sites to alter the gene expression profile, including the transcription of genes exclusively induced by IRF4 T95R but not by IRF4 WT . This previously undescribed multimorphic IRF4 pathophysiology disrupts normal lymphocyte biology, causing human disease.

Surface sediment concentration (SSC) is linked to several problems related to water quality and its monitoring is costly because of the required fieldwork and laboratory analyses. Thus, sediment measurements are often sporadic, punctual, and performed during a short period. Orbital remote sensing allows the monitoring of SSC along the river channel permitting continuous and spatial information. This work had two objectives: (1) to model the surface concentration of sediments in the main channel of the Doce river using data from Multispectral Instrument (MSI)/Sentinel 2 and Operational Land Imager (OLI)/Landsat 8 satellite sensors; and (2) to compare different linear modeling approaches to select the best variables for SSC monitoring. For comparison with actual field data, we used mean SSC measurements in 14 sediment gauge stations from 2013 to 2020. Reflectance data of the MSI/Sentinel 2 and OLI/Landsat 8 satellites bands and spectral indices related to the monitoring of water resources were used as explanatory variables. Simple and multiple linear regression models (SLR and MLR), least absolute shrinkage and selection operator (LASSO), and Elastic Net regression were used to predict the SSC. The near-infrared band images from both MSI/Sentinel 2 and OLI/Landsat 8 satellites showed a strong linear relationship with the SSC. Multiple linear regression, LASSO and Elastic Net regressions showed good performance for SSC prediction. Sediment flow maps show an SSC reduction in the Doce river channel in recent years, indicating that part of the material from the Fundão tailings dam rupture may have been transported through sediment resuspension and transport processes., 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 Ltd. All rights reserved.)

Background: Vilobelimab, an anti-C5a monoclonal antibody, was shown to be safe in a phase 2 trial of invasively mechanically ventilated patients with COVID-19. Here, we aimed to determine whether vilobelimab in addition to standard of care improves survival outcomes in this patient population., Methods: This randomised, double-blind, placebo-controlled, multicentre phase 3 trial was performed at 46 hospitals in the Netherlands, Germany, France, Belgium, Russia, Brazil, Peru, Mexico, and South Africa. Participants aged 18 years or older who were receiving invasive mechanical ventilation, but not more than 48 h after intubation at time of first infusion, had a PaO 2 /FiO 2 ratio of 60-200 mm Hg, and a confirmed SARS-CoV-2 infection with any variant in the past 14 days were eligible for this study. Eligible patients were randomly assigned (1:1) to receive standard of care and vilobelimab at a dose of 800 mg intravenously for a maximum of six doses (days 1, 2, 4, 8, 15, and 22) or standard of care and a matching placebo using permuted block randomisation. Treatment was not continued after hospital discharge. Participants, caregivers, and assessors were masked to group assignment. The primary outcome was defined as all-cause mortality at 28 days in the full analysis set (defined as all randomly assigned participants regardless of whether a patient started treatment, excluding patients randomly assigned in error) and measured using Kaplan-Meier analysis. Safety analyses included all patients who had received at least one infusion of either vilobelimab or placebo. This study is registered with ClinicalTrials.gov, NCT04333420., Findings: From Oct 1, 2020, to Oct 4, 2021, we included 368 patients in the ITT analysis (full analysis set; 177 in the vilobelimab group and 191 in the placebo group). One patient in the vilobelimab group was excluded from the primary analysis due to random assignment in error without treatment. At least one dose of study treatment was given to 364 (99%) patients (safety analysis set). 54 patients (31%) of 177 in the vilobelimab group and 77 patients (40%) of 191 in the placebo group died in the first 28 days. The all-cause mortality rate at 28 days was 32% (95% CI 25-39) in the vilobelimab group and 42% (35-49) in the placebo group (hazard ratio 0·73, 95% CI 0·50-1·06; p=0·094). In the predefined analysis without site-stratification, vilobelimab significantly reduced all-cause mortality at 28 days (HR 0·67, 95% CI 0·48-0·96; p=0·027). The most common TEAEs were acute kidney injury (35 [20%] of 175 in the vilobelimab group vs 40 [21%] of 189 in the placebo), pneumonia (38 [22%] vs 26 [14%]), and septic shock (24 [14%] vs 31 [16%]). Serious treatment-emergent adverse events were reported in 103 (59%) of 175 patients in the vilobelimab group versus 120 (63%) of 189 in the placebo group., Interpretation: In addition to standard of care, vilobelimab improves survival of invasive mechanically ventilated patients with COVID-19 and leads to a significant decrease in mortality. Vilobelimab could be considered as an additional therapy for patients in this setting and further research is needed on the role of vilobelimab and C5a in other acute respiratory distress syndrome-causing viral infections., Funding: InflaRx and the German Federal Government., Competing Interests: Declaration of interests NCR and RG are founders, active officers, and executive directors of the board, and hold shares and stock options in InflaRx. KP is the chief clinical development officer and holds stock options in InflaRx. RZ is the program director and holds stock options in InflaRx. SR is an employee of Metronomia Clinical Research and a contracted statistical service provider for InflaRx. MW receives grants from the German Research Foundation (SFB-TR84 C6, SFB-TR84 C9, and SFB 1449 B02) and German Ministry of Education and Research (e:Med CAPSyS [01ZX1304B], SYMPATH [01ZX1906A], NUM-NAPKON [01KX2021], and PROVID [01KI20160A]). APJV received consulting fees from InflaRx for advisory work, paid to the institution. GM received honoraria for lecturing and consulting from B Braun, 4TEEN4, Adrenomed, and Philips. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory., Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis., Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands)., Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness., Competing Interests: Potential conflicts of interest. All authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Species abundance distributions (SADs) link species richness with species abundances and are an important tool in the quantitative analysis of ecological communities. Niche-based and sample-based SAD models predict different spatial scaling properties of SAD parameters. However, empirical research on SAD scaling properties is largely missing. Here we extracted percentage cover values of all occurring vascular plants as proxies of their abundance in 1725 10-m 2 plots from the GrassPlot database, covering 47 regional data sets of 19 different grasslands and other open vegetation types of the Palaearctic biogeographic realm. For each plot, we fitted the Weibull distribution, a model that is able to effectively mimic other distributions like the log-series and lognormal, to the species-log abundance rank order distribution. We calculated the skewness and kurtosis of the empirical distributions and linked these moments, along with the shape and scale parameters of the Weibull distribution, to plot climatic and soil characteristics. The Weibull distribution provided excellent fits to grassland plant communities and identified four basic types of communities characterized by different degrees of dominance. Shape and scale parameter values of local communities on poorer soils were largely in accordance with log-series distributions. Proportions of subdominant species tended to be lower than predicted by the standard lognormal SAD. Successive accumulation of plots of the same vegetation type yielded nonlinear spatial scaling of SAD moments and Weibull parameters. This scaling was largely independent of environmental correlates and geographic plot position. Our findings caution against simple generalizations about the mechanisms that generate SADs. We argue that in grasslands, lognormal-type SADs tend to prevail within a wider range of environmental conditions, including more extreme habitats such as arid environments. In contrast, log-series distributions are mainly restricted to comparatively species-rich communities on humid and fertile soils., (© 2022 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Introduction: For many patients with primary immune deficiency (PID), stem-cell transplantation (SCT) may be life-saving., Objective: To review our experience of 11 years transplanting children with PID in Mexico., Methods: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis., Results: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD., Discussion: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors., (© 2022 The Scandinavian Foundation for Immunology.)

A solution of the constant cutting velocity problem of quick-return mechanisms is the main concern of this paper. An optimal sliding mode control in the task space is used to achieve uniform and accurate cuts throughout the workpiece. The switching hyperplane is designed to minimize the position error of the slider-dynamics in an infinite horizon. A Jacobian compensator is used to exploit the mechanical advantage and ensure controllability. The velocity profile is constructed in terms of the mechanism and workpiece geometric properties. Stability of the closed-loop dynamics is verified with the Lyapunov stability theory. Experiments are carried out in a quick-return mechanism prototype to validate the proposal., 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 © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

Transcatheter Aortic Valve Implantation (TAVI) or Replacement (TAVR) is a promising treatment for aortic valve stenosis, consisting of a procedure to replace a damaged native aortic valve by a bioprosthetic one. This replacement valve control the flow of blood using leaflets that are similar to the ones of a native aortic valve. Commonly manufactured using bovine or porcine pericardium, it is a tissue histologically composed of collagen fibers embedded into a nearly-isotropic matrix, where their distribution makes the pericardium behave as an anisotropic hyperelastic material. Because of such complicated behavior, bioprosthetic pericardium valves are, as expected, sensitive to the distribution and orientation of these fibers in such device. Therefore, the objective of this work is a thorough systematic study on the influence of these fibers' distribution. First, a Finite Element model of a bioprosthetic valve is generated; then, a material routine to accurately describe the behavior of pericardium is implemented in a commercial software package; in addition, a dedicated algorithm to specify the direction of fibers is developed. Finally, a systematic study on the influence that fiber orientations have on the overall behavior of the TAV is performed. As a result of this study, two extreme behaviors are highlighted depending on the preferential orientation of collagen fibers; namely, one with fibers in circumferential direction and the opposite with fibers in an axial orientation. Then, it is concluded that the behavior of fibers in circumferential direction is very sensitive to small variations of the orientation angle, whereas such orientation is not as determining when the aim is to achieve a behavior near to the one corresponding with axial orientation., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This work presents a non-invasive methodology to obtain a three-dimensional femur model of three-year-old infants affected with Osteogenesis Imperfecta (OI) type III. DICOM ® Files of a femur were processed to obtain a finite element model to assess the transverse, the oblique, and the comminuted fractures. The model is evaluated under a normal walking cycle. The loads applied were considered the most critical force generated on the normal walking cycle, and the analyses considered anisotropic bone conditions. The outcome shows stress concentration areas in the central zone of the diaphysis of the femur, and the highest levels of stress occur in the case of the comminuted fracture, while the transverse fracture presents the lowest values. Thus, the method can be helpful for determining the bone fracture behavior of certain pathologies, such as osteogenesis imperfecta, osteopenia, and osteoporosis.

Background: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern., Methods: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated., Results: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log 10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log 10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups., Conclusions: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.)., (Copyright © 2021 Massachusetts Medical Society.)

This study aimed to compare performance in working memory (WM), processing speed (PRS), and attention measures in children and adolescents with typical development (TD) and with Attention deficit hyperactivity disorder (inattentive [ADHD-I] or combined [ADHD-C]) presentations, and to determine the predictive ability of the measures mentioned to discriminate between ADHD presentations and TD. 260 children and adolescents, 138 with ADHD (70 ADHD-I and 68 ADHD-C) and 122 TD in two age cohorts (8-12 years; 13-16 years), were assessed with WM and PRS indexes of Wechsler Intelligence Scale for Children (WISC-IV) and the d2 attention test. Significant differences between ADHD and TD groups in the WISC-IV GAI scores were found in children but not in adolescents. Children and adolescents with both ADHD presentations performed poorly on the PRS index, while on the WM index only children exhibited difficulties. In the attention test, children with ADHD-C showed more impulsivity and more difficulties for processing speed, concentration and accuracy than ADHD-I and TD. In addition, both ADHD presentations had higher inattention scores than TD. ADHD adolescents performed worse than TD in processing speed, concentration and accuracy. ADHD groups showed more impulsivity and inattention than TD. Digit Span and Symbol Search (WISC-IV) and processing speed and accuracy (d2) successfully classified ADHD and TD in children, but in adolescents, only coding (WISC-IV) and accuracy (d2) successfully classified ADHD presentations and TD. The WISC-IV and d2 yield neuropsychological profiles which reflect age-related cognitive changes and may allow the adaptation of more tailored early interventions for ADHD.

Ultrafast lasers micromachining results depend on both the processing parameters and the material properties. The obtained thermal effects are negligible if a good combination of processing parameters is chosen. However, optimizing the processing parameters leading to the required surface quality on a given material can be quite complex and time consuming. We developed a semi-empirical model to estimate the heat accumulation on a surface as a function of the laser fluence, scanning speed and repetition rate. The simulation results were correlated with experimental ones on different materials, and compared with the transient temperature distributions calculated using an analytical solution to the heat transfer equation. The predictions of the proposed model allow evaluating the heat distribution on the surface, as well as optimizing the ultrafast laser micromachining strategy, yielding negligible thermal damage.

Introduction: Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe SARS-CoV-2 infection, the reported impact of COVID-19 in these patients has been reassuring, while the differential susceptibility of distinct types of IEI remains unclear., Objective: We aimed to describe the findings and outcomes of our known patients with IEI who were diagnosed with COVID-19., Methods: In a retrospective study from March 2020 to February 2021, four centers in Mexico collected clinical, laboratory, and genetic data from pediatric and adult patients with known diagnoses of IEI who presented with COVID-19, based on compatible symptoms and positive SARS-CoV-2 testing or known household exposure., Results: We report 31 patients with known IEI from Mexico who presented with SARS-CoV-2 infection. Seventy-four percent were male, 52% were pediatric, and 81% survived. Their ages ranged from 5 months to 56 years, with a median of 17 years. Sixty-five percent had predominant antibody deficiencies, 48% were hospitalized, and 26% required ICU. Pediatric patients had a higher hospital admission rate than adults. Inpatient mortality was 40%, and ICU mortality rate was 63%. Forty-eight percent developed pneumonia, while 36% had evidence of hyperinflammation (4 adults and 7 children). Predominant laboratory features were lymphopenia and thrombocytopenia, seen in 70 and 44% of patients, respectively. The serum D-dimer median value was 2.6 (0.5-20.6) μg/mL, and the median highest ferritin value was 1015 (32-10,303) ng/mL. Intravenous immunoglobulin was used in 80% of patients. Other treatments included macrolides (39%) and corticosteroids (29%). Six patients died from secondary infection or uncontrolled systemic inflammation., Discussion: Although impaired immunity due to IEI may be a predisposing factor for severe COVID-19, most of our patients with IEI who acquired the SARS-CoV-2 infection developed a well-tolerated infection and survived, as have more than 80% of worldwide reported patients to date. An impaired immune or inflammatory response may be a predisposing factor for some and a protective factor for others. A systematic review of the literature could help identify those patients at risk of severe disease and complications. Healthcare-associated infections should be aggressively prevented., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The derelict Remance gold mine is a possible source of pollution with potentially toxic elements (PTEs). In the study area, diverse mine waste has been left behind and exposed to weather conditions, and poses risks for soil, plants and water bodies, and also for the health of local inhabitants. This study sought to perform an ecological and health risk assessment of derelict gold mining areas with incomplete remediation, including: (i) characterizing the geochemical distribution of PTEs; (ii) assessing ecological risk by estimating the pollution load index (PLI) and potential ecological risk index (RI); (iii) assessing soil health by dehydrogenase activity; and iv) establishing non-carcinogenic (HI) and carcinogenic risks (CR) for local inhabitants. Soil health seems to depend on not only PTE concentrations, but also on organic matter (OM). Both indexes (PLI and RI) ranged from high to extreme near mining and waste accumulation sites. As indicated by both the HI and CR results, the mining area poses a health risk for local inhabitants and particularly for children. For this reason, it will be necessary to set up environmental management programs in the areas that are most affected (tailings and surrounding areas) and accordingly establish the best remediation strategies to minimize risks for the local population.

Biscutella auriculata L. is a plant that belongs to the Brassicaceae family and it has been found growing in a metal-contaminated area of the San Quíntín mine (Ciudad Real, Spain). The purpose of this work was to evaluate the mechanisms that allow this plant to tolerate high concentrations of copper. Seedlings were grown in a semi-hydroponic system for 15 days under 125 μM of Cu (NO 3 ) 2 . Exposure to copper resulted in growth inhibition and reduction in the photosynthetic parameters. Copper was mainly accumulated in vascular tissue and vacuoles of the roots and only a minor proportion was transferred to the shoot. Biothiol analysis showed a greater enhancement of reduced glutathione in leaves and increases of phytochelatins (PC2 and PC3) in both leaves and roots. Copper treatment induced oxidative stress, which triggered a response of the enzymatic and non-enzymatic antioxidant mechanisms. The results show that B. auriculata is able to tolerate high metal levels through the activation of specific mechanisms to neutralize the oxidative stress produced and also by metal sequestration through phytochelatins. The preferential accumulation of copper in roots provides clues for further studies on the use of this plant for phytostabilization and environmental recovery purposes in Cu-contaminated areas., (© 2020 Scandinavian Plant Physiology Society.)

People with Serious Mental Illness (SMI) could present risk behaviour that may lead to relapses. There are few instruments validated in our context to assess risk factors, but none takes into account several factors at the same time, and is specific for the risk of relapse. The objective of this work is to validate the Functional Analysis of Care Environments (FACE) Risk Profile into Spanish for people with SMI.

Background: The World Health Organization has reported that 1.35 million people die on the roads every year due to road traffic accidents. This paper focuses on exploring a passive safety system that reduces lesions in the overtaking run-over scenario., Methods: Head Injury Criterion (HIC) and Combined Thoracic Index (CTI) were evaluated through numerical simulations using LS-Dyna®; in order to compare the computed results, three different speed scenarios were carried out (velocity of running over 40, 50, 60 km/h)., Results: The computed results were divided into groups, A for the run-over test without a passive security system and B for the run-over test with a passive security system. For case A.1, the HIC15 was 3325. For case A.2, the HIC15 was 1510, and for case A.3, the HIC 15 was 1208. For case B.1, the HIC15 2605, for case B.2, the HIC15 was 1282, and for case B.3, the HIC was 730., Conclusion: The comparative results show that the passive safety system installed on the bicycle has an increased benefit impact on the severity of the injury on vulnerable road users, decreasing the probability of cranioencephalic lesions in all study cases. In addition, the thorax injuries are cut down only in the impact scenario at a speed of 40 km/h., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 E. H. López-García et al.)

Mining activities frequently leave a legacy of residues that remain in the area for long periods causing the pollution of surroundings. We studied on a 100 year-old mine, the behavior of potentially toxic elements (PTEs) and their ecotoxicological impact on activity and diversity of microorganisms. The PTEs contamination assessment allowed the classification of the materials as highly (reference- and contaminated-samples) and very highly polluted (illegal spill of olive mill wastes (OMW), tailings, and dumps). OMW presented the lowest enzymatic activities while tailings and dumps had low dehydrogenase and arylsulfatase activities. All the α-diversity indices studied were negatively impacted in dumps. Tailings had lower Chao1 and PD whole tree values as compared to those of reference-samples. β-diversity analysis showed similar bacterial community composition for reference- and contaminated-samples, significantly differing from that of tailings and dumps. The relative abundance of Gemmatimonadetes, Bacteroidetes, and Verrucomicrobia was lower in OMW, tailings, and dumps as compared to reference-samples. Fifty-seven operational taxonomic units were selected as responsible for the changes observed between samples. This study highlights that assessing the relationship between physicochemical properties and microbial diversity and activity gives clues about ongoing regulating processes that can be helpful for stakeholders to define an appropriate management strategy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: The aim of this study was to design and validate a questionnaire to analyze students' expectations, along with their level of interest and overall satisfaction with their nursing studies., Background: The expectations of students on entering university are closely related to the level of interest that they have in their area of study and their general satisfaction with it. This is certainly a conditioning factor in their learning. In this regard, there are few quantitative instruments that measure the expectations of first-year nursing students., Method: A mixed questionnaire was constructed using items validated in previous studies, along with new items formulated following a review of the literature. The questionnaire was validated with a sample of 339 first-year degree program nursing students., Results: The scales of expectations and degree of interest showed strong internal consistency (Cronbach's α > .7)., Conclusion: The questionnaire to evaluate the expectations and interest of students demonstrated satisfactory psychometric properties., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2020 National League for Nursing.)

This study employed multivariate statistical techniques in one of the main river basins in Brazil, the Doce River basin, to select and evaluate the most representative parameters of the current water quality aspects, and to group the stations according to the similarity of the selected parameters, for both dry and rainy seasons. Data from 63 qualitative monitoring stations, belonging to the Minas Gerais Water Management Institute network were used, considering 38 parameters for the hydrological year 2017/2018. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to reduce the total number of variables and to group stations with similar characteristics, respectively. Using PCA, four principal components were selected as indicators of water quality, explaining the cumulative variance of 68% in the rainy season and 65% in the dry season. The HCA grouped the stations into four groups in the rainy season and three groups in the dry season, showing the influence of seasonality on the grouping of stations. Moreover, the HCA made it possible to differentiate water quality stations located in the headwaters of the basin, in the main river channel, and near urban centers. The results obtained through multivariate statistics proved to be important in understanding the current water quality situation in the basin and can be used to improve the management of water resources because the collection and analysis of all parameters in all monitoring stations require greater availability of financial resources.

Monazite ((Ce, La, Nd, Th) PO 4 ) is a rare and strategic mineral that occurs naturally as an accessory and minor mineral in diverse igneous and metamorphic rocks. This mineral does not frequently form mineable ore deposits and it has different typologies, including those formed by endogenous processes (generally "yellow monazite" mineralizations) and those formed by exogenous processes ("gray monazite" mineralizations). The mineral is an important ore of Rare Earth Elements (REEs), which have been identified by the European Union as critical raw materials. Monazite can be considered a weathering-resistant mineral, and the mobility of the REE and associated elements is low. The study reported here concerns a mineralogical and geochemical assessment of the occurrence and risks associated with the presence of concentrations of monazite in a typical, well-developed, and representative red Mediterranean soil, in order to establish the associated risk with their future mining. The results confirmed that monazite ore is particularly poor in radioactive elements, and it is concentrated in the most surficial soil horizons. The chemical mobility of REEs present in the soil, as assessed by selective extraction with ammonium acetate in acidic media, follows the order Y > Dy > U > Tb > Gd > Eu > Sm > La > Th > Ce. The mobility of REEs contained in monazite proved to be higher than that of the REE compounds in the upper horizons of the soil profile suggesting the immobilization in other REE-containing minerals, while light REEs show lower mobility rates than heavy REEs, due to an immobilization of LREE by sorption with iron oxy-hydroxides. Further studies are required in order to obtain better speciation data for REEs in soils aimed to identify soluble and insoluble compounds.