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Previous studies suggested the role of cellular senescence in late-life depression (LLD). However, it is unclear how this finding relates to common features of LLD, such as medical and cognitive problems. We applied factor analyses to an extensive battery of clinical variables in 426 individuals with LLD. Here we tested the relationship between these factors, age and sex, with an index of cellular senescence based on 22 senescence-associated secretory phenotype proteins. We found four factors: 'depression and anxiety severity', 'cognitive functioning', 'cardiovascular and cardiometabolic health' and 'blood pressure'. A higher senescence-associated secretory phenotype index was associated with poorer 'cognitive functioning' and 'cardiovascular and cardiometabolic health' but not with 'depression and anxiety severity'. These findings highlight the role of cellular senescence in poorer physical and cognitive health in LLD. They are consonant with the viewpoint that co-occurring medical burdens and their associated disabilities are part of a phenotype of accelerated ageing in LLD., Competing Interests: E.J.L. is a consultant for Prodeo, IngenioRx, Pritikin ICR and Boehringer-Ingelheim, has a patent application for sigma-1 agonists in COVID-19 treatment and receives research support from PCORI, COVID Early Treatment Fund, Emergent Venture FastGrants and MagStim. J.F.K. reports receiving an honorarium from Otsuka for the preparation and presentation of a webinar (disease-state, not product focused), from NightWare and Biogen for scientific advising and potential equity from Aifred Health for scientific advising. B.H.M. holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He also receives compensation from the Centre for Addiction and Mental Health (CAMH) and the University of Toronto, Ontario. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study funded by CAMH Foundation) and HAPPYneuron (software used in a study funded by Brain Canada). Within the past 3 years, he has received research support from the Patient-Centered Outcomes Research Institute (PCORI), and he has been an unpaid consultant to Myriad Neuroscience. D.M.B. receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. He has been the site principal investigator for sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. The other co-authors do not have a conflict of interest related to this study.

Background: There is growing evidence of the anti-inflammatory effect of the anti-diabetic drug metformin and its use to reduce pain. However, we currently lack studies investigating whether metformin is associated with a reduction in chronic back pain prevalence when considering physical activity levels, body mass index (BMI), and age., Objective: To investigate whether use of metformin is associated with lower levels of reporting of chronic back pain in a large cohort with type 2 diabetes when stratified for physical activity, BMI, and age., Methods: This is a cross-sectional study of 21,889 participants with type 2 diabetes who were drawn from the UK Biobank database. We investigated whether people using metformin reported a higher prevalence of chronic low back pain than those who did not. Type 2 diabetes, chronic back pain, and metformin were self-reported. Participants were stratified according to their physical activity level (low, moderate and high), BMI (normal, overweight, and obese), and age (40 to <50; 50 to < 60; and ≥60 years). Logistic regression models were built for each physical activity level, BMI and age category to investigate the prevalence of chronic back pain amongst those using and not using metformin., Results: Participants who were using metformin and who had low levels of physical activity [OR 0.87, 95%CI 0.78 to 0.96] or who were obese [OR 0.90, 95%CI 0.86 to 0.98] or older [OR 0.85, 95%CI 0.78 to 0.93] had lower odds of reporting chronic back pain than their counterparts., Conclusion: The anti-diabetic drug metformin might reduce prevalence of chronic low back pain in people who are older, overweight, or less active. These findings should be confirmed in studies using a longitudinal design., Competing Interests: The authors have declared no competing interests exist., (Copyright: © 2023 Carvalho-e-Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Two epoxy resins with different viscosities were enhanced up to 1 wt.%, applying a simple method with carbon nanofibers (CNFs). These were characterized in terms of static bending stress, stress relaxation, and creep tests. In bending, the contents of 0.5 wt.% and 0.75 wt.% of CNFs on Ebalta and Sicomin epoxies, respectively, promote higher relative bending stress (above 11.5% for both) and elastic modulus (13.1% for Sicomin and 16.2% for Ebalta). This highest bending stress and modulus occurs for the lower viscosity resin (Ebalta) due to its interfacial strength and dispersibility of the fillers. Creep behaviour and stress relaxation for three stress levels (20, 50, and 80 MPa) show the benefits obtained with the addition of CNFs, which act as a network that contributes to the immobility of the polymer chains. A long-term experiment of up to 100 h was successfully applied to fit the Kohlrausch-Williams-Watts (KWW) and Findley models to stress relaxation and creep behaviour with very good accuracy.

We evaluated the mortality due to aspergillosis in free-ranging Magellanic penguins during their migration and the reproductive season. A total of 98 carcasses of penguins were collected along 370 km of coastline in Southern Brazil, between June 2017 and October 2019, and from reproductive colonies in Patagonian Argentina, in January 2019. All animals were necropsied, and only proven cases were computed. Aspergillosis was diagnosed in 2.5% of the penguins evaluated during their migration route. Our study, of the Southern coast of Brazil, is the first to demonstrate that aspergillosis is an important cause of mortality in free-ranging penguins. The implications of these findings in the One Health context are discussed., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion-dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty-five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2-MRI-liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron-related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Orchard net cover improves plant physiology, yield and fruit quality, pest and disease control, and anticipates fruit ripening. Moreover, this crop technology has been used to reduce natural cherry cracking (NCC). This is a serious physiological disorder that cracks the epidermis, the hypodermis, and the storage parenchyma layers of the fruit due to rainfall events near the harvest and it is related to low fruit osmotic potential and/or high fruit water permeability. This work aims to study the effect of orchard net cover on sweet cherry trees, cv. Early Bigi, in two harvesting years (2019 and 2021). The NCC, the induced cracking index (CI), and the cracking type incidence were determined. In addition, epicuticular and intra-cuticular wax content, biometric and physicochemical parameters were also evaluated. Net cover reduced the natural cracking index by 40%. High fruit weight values were observed in covered trees comparing to the control ones, with increases of 45% and 13%, in 2019 and 2021, respectively. A positive correlation was observed between CI and total soluble solids and a negative correlation between CI and wax content. Therefore, with forecasts of worsening heavy precipitation events near harvest, protecting cherry trees with nets will increase resistance to fruit cracking., Competing Interests: The authors declare no conflicts of interest.

Introduction: The use of the Cannabis sativa plant by man has been common for centuries due to its numerous therapeutic properties resulting from the compounds present in it, called cannabinoids. However, the use of these compounds as drugs is still limited due to the psychotropic effects caused by them. The proteins that act as receptors of cannabinoid compounds were identified and characterized, being called CB1 and CB2 receptors. There is a series of 50 cannabinoid compounds that was studied through quantum and chemometric methods in order to obtain a mathematical model that could relate the structure of these compounds to their psychotropic activity. That model proved to be effective by predicting the psychoactivity of the 50 compounds from the series and elucidating relevant characteristics that imply in psychoactivity. However, most of these 50 compounds do not have experimental data of biological activity with CB1 and CB2 receptors., Objectives: This study aims to generate QSAR models in order to predict the biological activity of the 50 cannabinoid compounds and then relate the predicted biological activity values to the already known psychoactivity., Methods: Another series of cannabinoid compounds was selected to generate and validate QSAR models, aiming to predict the biological activity of the 50 cannabinoid compounds with both CB1 and CB2 receptors., Results: The PLS-CB1 and PLS-CB2 QSAR models were generated and validated in this work, proving to be highly predictive, and the biological activities (pK ) of the 50 cannabinoid compounds were predicted by them. It is important to highlight compounds Ic14, Ic18, and Ic19 (psychotropic inactive) which presented higher predicted pK values than the main cannabinoid compounds (Δ9-THC and Δ8-THC). Also, compound Ic21 stood out as the highest value of the predicted biological activities in the interaction with the CB2 receptor., Conclusion: The generated PLS models and the predicted pK i values of the 50 cannabinoid compounds can provide valuable information in the drug design of new cannabinoid compounds that can interact with CB1 and CB2 receptors in a therapeutic way with no psychotropic effects., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Quantification of peritoneal protein loss (PPL) may be expressed according to a timely collection (24-h measurement or 4-h PET assessment) and as a concentration. The aim of this study was to compare the quantification methods of 24-h and 4-h collections., Methods: This study included 81 prevalent peritoneal dialysis patients. Demographics and clinical and bioelectrical impedance features were registered. PPL was measured (4-h PET and 24-h results) and peritoneal protein clearance was calculated. A linear regression model was performed., Results: Age and continuous ambulatory peritoneal dialysis (compared to cycler) were positively associated with greater PPL on 24-h collections. Neither cardiovascular disease, hypertension, diabetes nor the comorbidity Charlson Index was significantly associated with PPL. There was a consistent univariable relationship with D/P creatinine, whichever sampling method was used. Only 24-h measurements of PPL correlated with body composition variables. In multiple linear regression analysis, D/P creatinine association with PPL stands out. On the other hand, 24-h determinations (in grams or clearance) were associated with overhydration. PET protein quantification was associated with peritoneal creatinine clearance., Discussion/conclusion: Different methods sign different pathophysiological pathways. PET protein loss quantification should be regarded as a marker of peritoneal membrane intrinsic permeability. Measurements of a 24-h sample might be closer to patients' clinical status and prognosis, signalizing opportunities for therapy intervention., (© 2022 S. Karger AG, Basel.)

Objective: In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance., Design: This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals., Results: After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression., Conclusion: Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging., (Copyright © 2022 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The mechanical extraction of oils from Brazilian açaí ( Euterpe oleracea Mart) produces significant amounts of a byproduct known as "meal", which is frequently discarded in the environment as waste material. Nevertheless, plant byproducts, especially those from oil extraction, may contain residual polyphenols in their composition and be a rich source of natural bioactive compounds. In this study, the phenolic composition and in vitro biological properties of a hydroethanolic açaí meal extract were elucidated. The major compounds tentatively identified in the extract by high-resolution mass spectrometry were anthocyanins, flavones, and flavonoids. Furthermore, rhamnocitrin is reported in an açaí byproduct for the first time. The extract showed reducing power and was effective in scavenging the ABTS radical cation (820.0 µmol Trolox equivalent∙g -1 ) and peroxyl radical (975.7 µmol Trolox equivalent∙g -1 ). NF-κB activation was inhibited at 10 or 100 µg∙mL -1 and TNF-α levels were reduced at 100 µg∙mL -1 . However, the antibacterial effects against ESKAPE pathogens was not promising due to the high concentration needed (1250 or 2500 µg∙mL -1 ). These findings can be related to the diverse polyphenol-rich extract composition. To conclude, the polyphenol-rich extract obtained from açaí meal showed relevant biological activities that may have great applicability in the food and nutraceutical industries.

Biostimulants, such as glycine betaine (GB), are a sustainable way to boost productivity and quality in fruit crops, even in adverse environment conditions. Sweet cherry ( Prunus avium L.) is an important crop, which is very sensitive to abiotic stress. Known primarily for its fruits, its leaves are also rich in bioactive substances, which, however, still have no commercial value. There are no studies about the effects of GB exogenous application on biochemical parameters of sweet cherry leaves and few studies about effects in sweet cherry tree physiology. This study was conducted in a Portuguese sweet cherry commercial orchard. Lapins sweet cherry trees were treated with a commercial product based on GB, at two different concentrations (0.25% and 0.40%). The applications were performed at three different phenological stages, according to the BBCH ( Biologische Bundesanstalt, Bundessortenamt und Chemische Industrie ) scale: 77, 81 and 86 BBCH. Both GB treatments improved leaf water status, photosynthetic pigments, soluble solids content, total phenolic contents, and antioxidant activity, resulting in better leaf water status regulation, greater photosynthetic capacity, and higher antioxidant activity. These results shows that GB can benefit sweet cherry tree physiology and provide new opportunities for sweet cherry leaves valorisation.

Background: The cell cycle is a critical mechanism for proper cellular growth, development and viability. The p16 INK4a and p21 Waf1/Cip1 are important regulators of the cell cycle progression in response to internal and external stimuli (e.g., stress). Accumulating evidence indicates that the prefrontal cortex (PFC) is particularly vulnerable to stress, where stress induces, among others, molecular and morphological alterations, reflecting behavioral changes. Here, we investigated if the p16 INK4a and p21 Waf1/Cip1 expression are associated with behavioral outcomes., Methods: Prefrontal cortex mRNA and protein levels of p16 INK4A and p21 Waf1/Cip1 of mice (six independent groups of C57BL/6J, eight mice/group, 50% female) exposed from 0 to 35 days of chronic restraint stress (CRS) were quantified by qPCR and Western Blot, respectively. Correlation analyses were used to investigate the associations between cyclin-dependent kinase inhibitors (CKIs) expression and anxiety- and depression-like behaviors., Results: Our results showed that the PFC activated the cell cycle regulation pathways mediated by both CKIs p16 INK4A and p21 Waf1/Cip1 in mice exposed to CRS, with overall decreased mRNA expression and increased protein expression. Moreover, correlation analysis revealed that mRNA and protein levels are statistically significant correlated with anxiety and depressive-like behavior showing a greater effect in males than females., Conclusion: Our present study extends the existing literature providing evidence that PFC cells respond to chronic stress exposure by overexpressing CKIs. Furthermore, our findings indicated that abnormal expression of p16 INK4A and p21 Waf1/Cip1 may significantly contribute to non-adaptive behavioral responses., 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 Mendes-Silva, Prevot, Banasr, Sibille and Diniz.)

Forecasting is of utmost importance for the Tourism Industry. The development of models to predict visitation demand to specific places is essential to formulate adequate tourism development plans and policies. Yet, only a handful of models deal with the hard problem of fine-grained (per attraction) tourism demand prediction. In this paper, we argue that three key requirements of this type of application should be fulfilled: (i) recency-forecasting models should consider the impact of recent events (e.g. weather change, epidemics and pandemics); (ii) seasonality-tourism behavior is inherently seasonal; and (iii) model specialization-individual attractions may have very specific idiosyncratic patterns of visitations that should be taken into account. These three key requirements should be considered explicitly and in conjunction to advance the state-of-the-art in tourism prediction models. In our experiments, considering a rich set of indoor and outdoor attractions with environmental and social data, the explicit incorporation of such requirements as features into the models improved the rate of highly accurate predictions by more than 320% when compared to the current state-of-the-art in the field. Moreover, they also help to solve very difficult prediction cases, previously poorly solved by the current models. We also investigate the performance of the models in the (simulated) scenarios in which it is impossible to fulfill all three requirements-for instance, when there is not enough historical data for an attraction to capture seasonality. All in all, the main contributions of this paper are the proposal and evaluation of a new information architecture for fine-grained tourism demand prediction models as well as a quantification of the impact of each of the three aforementioned factors on the accuracy of the learned models. Our results have both theoretical and practical implications towards solving important touristic business demands., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Khatibi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Coronavirus disease 2019 (COVID-19) may cause clinical manifestations that last for weeks or months after hospital discharge. The manifestations are heterogeneous and vary in their frequency. Their multisystem nature requires a holistic approach to management. There are sparse data from the South Asian region on the outcomes of hospital-discharged COVID-19 patients. We assessed the posthospital discharge outcomes of a cohort of Sri Lankan COVID-19 patients and explored the factors that influenced these outcomes., Methods: Data were prospectively collected from patients who were discharged following an admission to the Nawaloka Hospital, Sri Lanka with COVID-19 from March to June 2021. At discharge, their demographic, clinical and laboratory findings were recorded. The patients were categorised as having mild, moderate and severe COVID-19, based on the Sri Lanka Ministry of Health COVID-19 guidelines. Following discharge, information on health status, complications and outcomes was collected through clinic visits and preplanned telephone interviews. A validated (in Sri Lanka) version of the Short Form 36 health survey questionnaire (SF-36) was used to assess multi-item dimensions health status of the patients at 1, 2 and 3 mo postdischarge., Results: We collected data on 203 patients (male, n=111 [54.7%]). The level of vaccination was significantly associated with disease severity (p<0.001). Early recovery was seen in the mild group compared with the moderate and severe groups. At 3 mo, on average 98% of mild and 90% of moderate/severe patients had recovered. Based on the SF-36, physical functioning dimensions, role limitation due to physical and emotional health, energy/ fatigue, emotional well-being, social functioning, pain and general health were significantly different in the moderate/severe vs mild COVID-19 groups at 1, 2 and 3 mo postdischarge (p<0.05). Twenty-three patients developed complications, of which the most common were myocardial infarction with heart failure (n=6/23; 26.1%), cerebrovascular accident (n=6/23; 26.1%) and respiratory tract infections (n=3/23; 13.01%) and there were six deaths., Conclusions: In our cohort, receiving two doses of the COVID-19 vaccine was associated with reduced disease severity. Those with mild disease recovered faster than those with moderate/severe disease. At 3 mo posthospital discharge, >90% had recovered., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Vitamin E comprises compounds consisting of a chromanol ring and an isoprenoid side-chain, and is an essential lipid-soluble nutrient with several physiological functions. Vitamin E intake has been reported as inadequate for some populations. Only a fraction of dietary vitamin E is effectively released from the food matrix (bioaccessible fraction), absorbed (enterocyte uptake/epithelial transport) and transported in lipoproteins to reach the target tissues (bioavailable fraction), depending on the food structure, composition, and processing. Therefore, research concerning the fate of vitamin E through the gastrointestinal tract is of paramount importance for developing healthy foods and guiding effective public policies. The combination of simulated in vitro gastrointestinal digestion followed by intestinal epithelial transport and/or enterocyte uptake assays using ex vivo cell models has been successfully used to mimic the physiological conditions and predict the bioaccessibility and epithelial transport of compounds. The objective of this review was to summarize the current knowledge and challenges for predicting the bioaccessibility and uptake/epithelial transport of vitamin E by in vitro and ex vivo assays. Here, we revisited the metabolism of vitamin E and introduced in vitro and ex vivo methods for estimating the bioaccessibility and intestinal absorption of vitamin E. This review compiles data on vitamin E bioaccessibility in vitro and uptake/epithelial transport ex vivo for different food matrices, and discusses the factors that can affect their measurement. Additionally, co-culture approaches using hepatic lineages to assess vitamin E bioavailability are further presented., 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: Cocoa is an important tropical tree crop that is mainly cultivated in agroforestry systems (AFS). This system, known as cabruca in northeastern Brazil, holds promise to reconcile biodiversity conservation and economic development. However, since cocoa AFS alters forest structure composition, it can affect litter dynamics in riparian zones and streams. Thus, our objective was to determine litter inputs and standing stocks in riparian zones and streams under three types of forest: managed cocoa AFS, abandoned cocoa AFS, and secondary forest., Methods: We determined terrestrial litter fall (TI), vertical (VI) and lateral (LI) litter inputs to streams, and litter standing stocks on streambeds (BS) in the Atlantic Forest of northeastern Brazil. Litter was collected every 30 days from August 2018 to July 2019 using custom-made traps. The litter was dried, separated into four fractions (leaves, branches, reproductive organs, and miscellaneous material) and weighed., Results: Terrestrial litter fall was similar in all forests, ranging from 89 g m -2 month -1 in secondary forest (SF) to 96 g m -2 month -1 in abandoned cocoa AFS (AC). Vertical input were higher in AC (82 g m -2 month -1 ) and MC (69 g m -2 month -1 ) than in SF (40 g m -2 month -1 ), whereas lateral input were higher in MC (43 g m -2 month -1 ) than in AC (15 g m -2 month -1 ) and SF (24 g m -2 month -1 ). Standing stocks followed the order SF > AC > MC, corresponding to 425, 299 and 152 g m -2 . Leaves contributed most to all litter fractions in all forests. Reproductive plant parts accounted for a larger proportion in managed AFS. Branches and miscellaneous litter were also similar in all forests, except for higher benthic standing stocks of miscellaneous litter in the SF. Despite differences in the amounts of litter inputs and standing stocks among the forests, seasonal patterns in the abandoned AFS (AC) were more similar to those of the secondary forest (SF) than the managed AFS, suggesting potential of abandoned AFS to restore litter dynamics resembling those of secondary forests., Competing Interests: The authors declare that they have no competing interests., (© 2022 Rialli Santos Brandão et al.)

Three-level data structures arising from repeated measures on individuals clustered within larger units are common in health research studies. Missing data are prominent in such studies and are often handled via multiple imputation (MI). Although several MI approaches can be used to account for the three-level structure, including adaptations to single- and two-level approaches, when the substantive analysis model includes interactions or quadratic effects, these too need to be accommodated in the imputation model. In such analyses, substantive model compatible (SMC) MI has shown great promise in the context of single-level data. Although there have been recent developments in multilevel SMC MI, to date only one approach that explicitly handles incomplete three-level data is available. Alternatively, researchers can use pragmatic adaptations to single- and two-level MI approaches, or two-level SMC-MI approaches. We describe the available approaches and evaluate them via simulations in the context of three three-level random effects analysis models involving an interaction between the incomplete time-varying exposure and time, an interaction between the time-varying exposure and an incomplete time-fixed confounder, or a quadratic effect of the exposure. Results showed that all approaches considered performed well in terms of bias and precision when the target analysis involved an interaction with time, but the three-level SMC MI approach performed best when the target analysis involved an interaction between the time-varying exposure and an incomplete time-fixed confounder, or a quadratic effect of the exposure. We illustrate the methods using data from the Childhood to Adolescence Transition Study., (© 2021 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

The use of model organisms is important for basic and applied sciences. Several laboratory species of fishes are used to develop advanced technologies, such as the zebrafish ( Danio rerio ), the medaka ( Oryzias latipes ), and loach species ( Misgurnus spp . ). However, the application of these exotic species in the Neotropical region is limited due to differences in environmental conditions and phylogenetic distances. This situation emphasizes the establishment of a model organism specifically for the Neotropical region with the development of techniques that may be applicable to other Neotropical fish species. In this work, the previous research efforts are described in order to establish the yellowtail tetra Astyanax altiparanae as a model laboratory species for both laboratory and aquaculture purposes. Over the last decade, starting with artificial fertilization, the yellowtail tetra has become a laboratory organism for advanced biotechnology, such as germ cell transplantation, chromosome set manipulation, and other technologies, with applications in aquaculture and conservation of genetic resources. Nowadays, the yellowtail tetra is considered the most advanced fish with respect to fish biotechnology within the Neotropical region. The techniques developed for this species are being used in other related species, especially within the characins class., Competing Interests: GY and JS were employed by Peixetec Biotecnologia Em Organismos Aquáticos LTDA. NV was employed by China Three Gorges Corp. The remaining 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 Yasui, Ferreira do Nascimento, Pereira-Santos, Santos Silva, Coelho, Visintin, Porto-Foresti, Okada Nakaghi, Vianna, Carvalho, Monzani, López and Senhorini.)

Background: It was verified the level of religiosity and spirituality, and symptoms of depression, stress, and anxiety of caregivers of children and adolescents with type 1 diabetes, and its interference in glycaemic control., Methods: Socio-economic and demographic data were collected from caregivers of 59 children and adolescents with type 1 diabetes and obtained dosages of fasting glucose (FG); postprandial glycaemia (PPG); fructosamine (FRUTO); and HbA1c, as well as the glycaemic variability-∆HbA1c. Levels of religiosity were obtained by the DUREL scale; the use of religious/spiritual coping was verified by the SRCOPE-Brief scale. Symptoms of depression, anxiety, and stress were analysed by the DASS-21 scale. The correlations between the variables were analysed by the Pearson coefficient, with significance at 5% level., Results: Inverse correlations were observed between caregivers' schooling with PPG (r = -0.30; P = 0.002) and FRUTO (r = -0.34; P = 0.008) and between family income and FRUTO (r = -0.37; P = 0.004). Direct, moderate correlations were observed between negative religious/spiritual coping (NSRCOPE) with symptoms of depression (r = 0.588; P < 0.0001), stress (r = 0.500; P < 0.0001), and anxiety (r = 0.551; P < 0.0001)., Conclusion: The direct association between NSRCOPE with symptoms of depression, stress, and anxiety was the highlighted item in the present study emphasizing the need for greater attention to the emotional health of informal caregivers of children and adolescents with DM1. It is necessary to reflect on the religious/spiritual support especially for the main caregiver of children and adolescents with DM1., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To improve almond performance under water limitations, the use of algae-based biostimulants may become a useful tool to reduce drought stress. However, besides possible effects on plant behavior, changes in fruit characteristics must also be considered. In this work, a preliminary study on the effect of two levels of an Ascophyllum nodosum -based biostimulant in the chemical characteristics of fruits from rain-fed cv. Marinada almond trees was carried out. The use of the recommended manufacturer's dosage resulted in a decreased content of soluble sugars and proteins when compared to the use of half the recommended dosage and the control assays (water only). Similarly, and although no significant differences were recorded, the content of bioactive compounds (ortho-diphenols, total phenolics, and flavonoids) tended to increase in non-treated trees. Finally, sensory analysis of treated and non-treated fruits did not record any changes in the perceived attributes, showing that no negative effects on consumers' acceptance will be caused by the application of this product. Long-term studies are needed to further confirm these results, also aimed at the monitoring of leaf gas exchange and water status parameters of trees.

Different climatic conditions are known to affect the synthesis of primary and secondary metabolites. Therefore, the phenolic contents in new growing areas could affect the quality and flavor of hazelnuts. The aim of this study was to determine the variability of the phenolic contents of the kernels in different commercial hazelnut cultivars depending on their growing area. Five cultivars ('Tonda Gentile delle Langhe', 'Merveille de Bollwiller', 'Pauetet', 'Tonda di Giffoni', and 'Barcelona' (syn. 'Fertile de Coutard')) grown in different European collection orchards were included in the study. High-performance liquid chromatography coupled with mass spectrometry was used to identify and quantify the phenolic compounds. Thirteen phenols were identified in the hazelnut kernels, including 7 flavanols, 2 hydroxybenzoic acids, 3 flavonols, and one dihydrochalcone. Catechin and procyanidin dimers were the main phenolic compounds found in the hazelnut kernels. The highest contents of catechin and total flavanols were determined in cultivars cultivated in Spain and northern Italy, and the lowest in Slovenia and France. Flavanols were the major phenolic groups independent of the place of cultivation, as they accounted for more than 50% of all phenolic compounds identified. The flavanols were followed by hydroxybenzoic acids, flavonols, and dihydrochalcones. Higher contents of flavanols and flavonols were found in kernels from areas characterized by higher natural irradiation, which stimulates their accumulation. The contents of hydroxybenzoic acids correlated with altitude, which stimulated phenolic acid synthesis. A negative correlation was observed between the dihydrochalcone content and annual rainfall, probably due to hydric stress.

The aim of this study was to evaluate the age and post-prandial variations in selected metabolite concentration that may indicate a shift in metabolism, from pre- to functional ruminant, according to the liquid diet fed to dairy calves. Sixteen newborn Holstein calves were included in the study in a randomized complete block experimental design. The calves were individually housed and fed 6 L/d with whole milk (WM) or milk replacer (MR). Blood samples were collected weekly at 0 h (before feeding), 1 h, 2 h, 4 h, and 8 h after morning feeding to evaluate glucose, β-hydroxybutyrate (BHB), fructosamine, total protein, and albumin. Calves fed WM had higher performance (p < 0.01) than did calves fed MR. The different liquid diets did not affect the average concentrations of plasma glucose. However, BHB was higher for WM-fed calves (p < 0.01). The concentration of plasma glucose reached the highest concentration at 1 and 4 hours after feeding WM or MR, respectively. Thus, these would be the most appropriate sampling times to study the glycemic status of calves according to the liquid diet fed. Fructosamine did not prove to be an informative metabolite to understand the shift in metabolism, as a function of rumen development, due to a small reduction as a function of age and a sampling time effect.

Depression is a complex and multifactorial disease, affecting about 6.5% of the elderly population in what is referred to as late-life depression (LLD). Despite its public health relevance, there is still limited information about the molecular mechanisms of LLD. We analyzed the blood plasma of 50 older adults, 19 with LLD and 31 controls, through untargeted mass spectrometry, and used systems biology tools to identify biochemical pathways and biological processes dysregulated in the disease. We found 96 differentially expressed proteins between LLD patients and control individuals. Using elastic-net regression, we generated a panel of 75 proteins that comprises a potential model for determining the molecular signature of LLD. We also showed that biological pathways related to vesicle-mediated transport and voltage-dependent calcium channels may be dysregulated in LLD. These data can help to build an understanding of the molecular basis of LLD, offering an integrated view of the biomolecular alterations that occur in this disorder. SIGNIFICANCE: Major depressive disorder in the elderly, called late-life depression (LLD), is a common and disabling disorder, with recent prevalence estimates of 6.5% in the general population. Despite the public health relevance, there is still limited information about the molecular mechanisms of LLD. The findings in this paper shed light on LLD heterogeneous biological mechanisms. We uncovered a potential novel biomolecular signature for LLD and biological pathways related to this condition which can be targets for the development of novel interventions for prevention, early diagnosis, and treatment of LLD., Competing Interests: Declaration of Competing Interest All authors have read the journal's policy on disclosure of potential conflicts of interest. All authors have disclosed any financial or personal relationship with organizations that could potentially be perceived as influencing the described research., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The demand for high-strength steel welds, as observed in civil and transport engineering, is related to a mass reduction in vehicles. Container-type trucks are examples of this kind of transport means because their boxes are able to be produced using Hardox grade steels. Therefore, this study reflects on the properties of welds in the MAG welding of Hardox 450, obtained through an innovative micro-jet cooling process with helium. This joining technology aims to reduce the formation of defects and to obtain a joint with very good assumed mechanical properties. Structural components of grade steel require welds with acceptable mechanical parameters with respect to operational loading conditions. That is, this study focuses on selecting welding parameters for the Hardox 450 steel and determining the weld quality with respect to microstructural observations and mechanical tests, such as the Charpy, tensile and fatigue tests. Weld fracturing under increasing monotonic force was examined and was strongly related to both stress components, i.e., axial and shear. The joint response under fatigue was expressed through differences in the fracture zones, i.e., at a stress value lower than the proportional limit, and weld degradation occurred in the shear and axial stress components. The data indicate that the hourglass specimen, with the weld in the centre zone of the measurement section, can be directly used to determine a weld response under cyclic loading. The impact test results showed attractive behaviour in the tested joint, as represented by 47 J at -20 °C. The recommended MAG welding parameters for Hardox 450 steel are low-oxygen when using an Ar + 18% CO 2 shielding mixture. The collected results can be directly used as a guide to weld thin-walled structures (6 mm) made of Hardox grade steel, while the data from mechanical tests can support the modelling, designing and manufacturing of components made from this kind of steel grade.

Background: A growing number of studies have reported a close relationship between high serum calcium (Ca)/low serum magnesium (Mg) and vascular calcification. Endothelial dysfunction and vascular inflammation seem plausible risk factors for the enhanced progression of kidney disease. The aim of this study was to evaluate the role of the Ca/Mg ratio as a predictor of the early onset of renal replacement therapy (RRT). Methods: This was a prospective study conducted in an outpatient low-clearance nephrology clinic, enrolling 693 patients with stages 4−5 of CKD. Patients were divided into two groups according to the start of renal replacement therapy (RRT). Results: The kidney’s survival at 120 months was 60% for a Ca−Mg ratio < 6 and 40% for a Ca−Mg ratio ≥ 6 (p = 0.000). Patients who started RRT had lower levels of Hb, Ca, Mg, albumin, and cholesterol and higher values of phosphorus, the Ca/Mg ratio, and PTH. High values of phosphorus and the Ca/Mg ratio and low levels of Mg and GFR were independent predictors of entry into RRT. A high Ca/Mg ratio, high phosphorus levels, and low levels of GFR were associated with a cumulative risk for initiation of RRT. Conclusions: In our population, the Ca/Mg ratio is an independent predictive factor for the initiation of a depurative technique.

Studies have shown that β-glucans extracted from the cell wall of cereals, algae, and yeasts have been associated with improved immune function. However, it is unknown whether algae β-glucan supplementation affects the performance, blood metabolites, or cell counts of immune cells in dairy calves. The objective of this randomized clinical trial was to evaluate whether supplementation of β-glucans to milk replacer in dairy calves fed 6 L/d improved growth performance and fecal status and altered the blood metabolite profile. In this trial, we enrolled Holstein calves (n = 34) at birth (body weight 36.38 ± 1.33 kg; mean ± standard deviation) to receive, from 1 d of age, either 2 g/d algae β-glucans mixed into 6 L/d of milk replacer (22.4% crude protein and 16.2% fat) or an unsupplemented milk replacer (control). The calves were blocked in pairs according to birth weight, sex, and date of birth (up to 5 d difference). Calves were housed individually, and calf starter (24.7% crude protein and 13.9% neutral detergent fiber) was offered ad libitum based on orts of the previous day until 56 d of age (end of the trial). Body weight was measured weekly, and health checks and daily fecal consistency were evaluated daily in every calf by the same observer. Calves with 2 consecutive days of loose feces that sifted through bedding were considered diarrhea positive. We used a linear mixed effects model to evaluate the effects of β-glucan supplementation fed during the preweaning period on performance (average daily gain), final weight, feed efficiency (FE), white blood cell count, and selected blood metabolites, repeated by time. A generalized linear mixed effects model was also run to evaluate the likelihood of a diarrhea bout in the first 28 d of life, controlling for the calf as the subject with a logistic distribution. We included age, serum total protein at 48 h, and birth weight as covariates. At 56 d, β-glucan-supplemented calves weighed more than control calves (56.3 vs. 51.5 kg). Treatment had no effect on total starter intake, but there was a treatment by age interaction for FE, with greater FE for β-glucan-supplemented calves in wk 3 and 5 of age. There was only a tendency for average daily gain to be greater in supplemented calves than in control calves for the duration of the study. Furthermore, control calves had 14.66 [95% confidence interval (95% CI): 9.87-21.77] times greater odds of having a diarrheal bout than β-glucan-supplemented calves. Control calves had 12.70 (95% CI: 8.82-18.28) times greater odds of having an additional day with an abnormal fecal score compared with β-glucan-supplemented calves, suggesting that supplementation ameliorated diarrhea severity. We found no association of treatment with concentrations of serum total protein, albumin, creatinine, or glucose during the preweaning period. Our findings suggest that dietary supplementation of 2 g/d of algae β-glucans to milk replacer improved fecal status and may affect growth, as evidenced by a higher weaning weight, compared with control calves. Future studies should explore the effect of algae β-glucans on lower-gut physiology and digestibility in dairy calves., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This study aimed to evaluate the effect of two liquid diets and the use of environmental enrichment (EE) in individually housed calves fed in open buckets. The treatments were arranged in a 2 × 2 factorial design, with factor 1 as the liquid diets: Whole Milk (WM) or Milk Replacer (MR); and factor 2 as absence or presence of environmental enrichment (brushes and a dry teat). Twenty-four newborn Holstein calves were distributed in four treatments: (1) WM; (2) WM + EE; (3) MR; and (4) MR + EE. Calves had free access to water and calf starter concentrate and were fed in a step-up/step-down feeding program and were weaned at 56 days of age. There was no effect of the association of different liquid diets with EE on the performance of the animals. The association of liquid diet with EE did not affect metabolic parameters, but WM-fed calves had higher concentrations of β-hydroxybutyrate (P < 0.05). Likewise, the interaction of liquid diet and EE did not affect the faecal score (P > 0.05), but animals fed with MR had more fluid faeces (P < 0.05). There was no change in the animals' behavioural repertoire as a function of liquid diets associated with EE. The animals used the EE approximately 1.4% of the time only and vocalized for 1.7% or performed non-nutritive feeding for 1.9%. There was a tendency (P < 0.06) for a reduction in vocalization by EE availability. However, the possibility of improved animal welfare using environmental enrichment is not ruled out since the animals vocalized less during the weaning process., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The Shoulder Pain and Disability Index (SPADI) is a measuring instrument for pain and disability in patients with shoulder dysfunction. However, its structure is controversial (ie, 1 or 2 domains)., Purpose: To investigate the structural validity of the Brazilian version of the SPADI in patients with chronic shoulder pain., Study Design: Cross-sectional study., Methods: Brazilian Portuguese speakers of both genders aged 18 years or older with shoulder pain for at least 90 days (chronic) were included in this study. The structure of the SPADI was assessed by means of exploratory factor analysis with the implementation of parallel analysis and by confirmatory factor analysis. For the latter, the following goodness-of-fit indices were considered: root mean square error of approximation with 90% confidence interval, comparative fit index, Tucker-Lewis index, standardized root mean square residual, and chi-square/degrees of freedom., Results: A total of 103 participants were included in the study. The original version of the SPADI with 2 domains and 13 items showed high covariance between domains (0.98), suggesting one-dimensionality. After exploratory factor analysis with the implementation of parallel analysis, one-dimensionality was found in the SPADI. Comparing models with 1 and 2 domains by means of confirmatory factor analysis, both presented adequate values (chi-square/degrees of freedom < 3; comparative fit index and Tucker-Lewis index > 0.90; root mean square error of approximation and standardized root mean square residual < 0.08). However, the model with one domain is more suitable for presenting lower values of Akaike information criterion (3308.713) and Bayesian information criterion (3377.216)., Conclusion: The Brazilian version of the SPADI has a one-dimensional structure with 13 items ("shoulder impairment" construct), in contrast to the version with 2 domains., (Copyright © 2021 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

Context: The establishment of pregnancy in cows requires uterine activity regulation of the main Hippo signalling effector yes-associated protein 1 (YAP). It remains unknown (1) how YAP activity at the corpus luteum (CL) correlates with early pregnancy-related events in ruminants; and (2) if YAP activity in the uterus and CL can be affected by metabolic disorders that may lead to pregnancy failure in ruminants., Aims and Methods: To determine the effect of early pregnancy on total and phospho-YAP expression and its transcriptional activity in the CL, we compared non-pregnant vs pregnant ewes. To understand the YAP activity dysregulation with disorders that may result in pregnancy loss, we induced negative energy balance in pregnant ewes., Key Results and Conclusions: Our main results indicate that early pregnancy alters the expression and activity patterns of YAP in the ovine CL but not in the endometrium. In addition, while our NEB-induced model fails to alter YAP activity at the endometrium level, we found that fasting during the first but not second week of pregnancy affects YAP activity in the CL of pregnant ewes., Implications: The data presented herein provide considerable insight into the activity of a signalling pathway that may be a key player in pregnancy recognition and establishment in ewes.

Three-level data arising from repeated measures on individuals clustered within higher-level units are common in medical research. A complexity arises when individuals change clusters over time, resulting in a cross-classified data structure. Missing values in these studies are commonly handled via multiple imputation (MI). If the three-level, cross-classified structure is modeled in the analysis, it also needs to be accommodated in the imputation model to ensure valid results. While incomplete three-level data can be handled using various approaches within MI, the performance of these in the cross-classified data setting remains unclear. We conducted simulations under a range of scenarios to compare these approaches in the context of an acute-effects cross-classified random effects substantive model, which models the time-varying cluster membership via simple additive random effects. The simulation study was based on a case study in a longitudinal cohort of students clustered within schools. We evaluated methods that ignore the time-varying cluster memberships by taking the first or most common cluster for each individual; pragmatic extensions of single- and two-level MI approaches within the joint modeling (JM) and the fully conditional specification (FCS) frameworks, using dummy indicators (DI) and/or imputing repeated measures in wide format to account for the cross-classified structure; and a three-level FCS MI approach developed specifically for cross-classified data. Results indicated that the FCS implementations performed well in terms of bias and precision while JM approaches performed poorly. Under both frameworks approaches using the DI extension should be used with caution in the presence of sparse data., (© 2022 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

The COVID-19 pandemic has particularly affected older adults residing in nursing homes, resulting in high rates of hospitalisation and death. Here, we evaluated the longitudinal humoral response and neutralising capacity in plasma samples of volunteers vaccinated with different platforms (Sputnik V, BBIBP-CorV, and AZD1222). A cohort of 851 participants, mean age 83 (60-103 years), from the province of Buenos Aires, Argentina were included. Sequential plasma samples were taken at different time points after vaccination. After completing the vaccination schedule, infection-naïve volunteers who received either Sputnik V or AZD1222 exhibited significantly higher specific anti-Spike IgG titers than those who received BBIBP-CorV. Strong correlation between anti-Spike IgG titers and neutralising activity levels was evidenced at all times studied (rho=0.7 a 0.9). Previous exposure to SARS-CoV-2 and age <80 years were both associated with higher specific antibody levels. No differences in neutralising capacity were observed for the infection-naïve participants in either gender or age group. Similar to anti-Spike IgG titers, neutralising capacity decreased 3 to 9-fold at 6 months after initial vaccination for all platforms. Neutralising capacity against Omicron was between 10-58 fold lower compared to ancestral B.1 for all vaccine platforms at 21 days post dose 2 and 180 days post dose 1. This work provides evidence about the humoral response and neutralising capacity elicited by vaccination of a vulnerable elderly population. This data could be useful for pandemic management in defining public health policies, highlighting the need to apply reinforcements after a complete vaccination schedule., 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 Rodriguez, Silva, Miglietta, Rall, Pascuale, Ballejo, López Miranda, Ríos, Ramis, Marro, Poncet, Mazzitelli, Salvatori, Ceballos, Gonzalez Lopez Ledesma, Ojeda, Aguirre, Miragaya, Gamarnik, Rossi, Laboratorio SeVa Group and PAMI Group.)

Objective: To evaluate the performance of the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis (F2) compared with transient elastography (TE), among chronic transfusion-dependent beta-thalassaemia (TDT) patients in a resource-poor setting., Design: A cross-sectional study., Setting: Adolescent and Adult Thalassaemia Care Centre (University Medical Unit), Kiribathgoda, Sri Lanka., Participants: 45 TDT patients who had undergone more than 100 blood transfusions with elevated serum ferritin >2000 ng/mL were selected for the study. Patients who were serologically positive for hepatitis C antibodies were excluded., Outcome Measures: TE and FIB-4 scores were estimated at the time of recruitment in all participants. Predefined cut-off values for F2, extracted from previous TE and FIB-4 scores studies, were compared. A new cut-off value for the FIB-4 score was estimated using receiver operating characteristics curve analysis to improve the sensitivity for F2 prediction., Results: Of the selected 45 TDT patients, 22 (49%) were males. FIB-4 score showed a significant linear correlation with TE (r=0.52;p<0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand, it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4, we improved the pick-up rate of F2 to 72%., Conclusions: Regardless of the cut-off point, the FIB-4 score cannot be used as a good screening tool to pick up F2 in patients with TDT, irrespective of their splenectomy status. On the contrary, at a 1.3 cut-off value, though FIB-4 is a very poor detector for F2 fibrosis, it will not erroneously diagnose F2 fibrosis in those who do not have it., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Infectious bronchitis virus (IBV) is a highly variable RNA virus that affects chickens worldwide. Due to its inherited tendency to suffer point mutations and recombination events during viral replication, emergent IBV strains have been linked to nephropathogenic and reproductive disease that are more severe than typical respiratory disease, leading, in some cases, to mortality, severe production losses, and/or unsuccessful vaccination. QX and DMV/1639 strains are examples of the above-mentioned IBV evolutionary pathway and clinical outcome. In this study, our purpose was to systematically compare whole genomes of QX and DMV strains looking at each IBV gene individually. Phylogenetic analyses and amino acid site searches were performed in datasets obtained from GenBank accounting for all IBV genes and using our own relevant sequences as a basis. The QX dataset studied is more genetically diverse than the DMV dataset, partially due to the greater epidemiological diversity within the five QX strains used as a basis compared to the four DMV strains from our study. Historically, QX strains have emerged and spread earlier than DMV strains in Europe and Asia. Consequently, there are more QX sequences deposited in GenBank than DMV strains, assisting in the identification of a larger pool of QX strains. It is likely that a similar evolutionary pattern will be observed among DMV strains as they develop and spread in North America.

A first step for microorganisms to reach the respiratory system and cause infectious disease is colonization in the nasopharynx. Humans inhale a bacterial load of up to 10 6 per cubic meter of air per day [1], including transient microorganisms between the upper and lower airways. This can lead to lung infections, amounting to billions of dollars in annual direct treatment costs in the United States, depending on the etiologic agent [2,3]. Curcumin has been described as a photosensitizer (PS) that, activated at 450 nm, is efficient against planktonic bacteria [4] and biofilms [5]. At the same time, effects on microbial interactions are commonly detected in the upper respiratory tract and should be considered for the treatment of adenoids [6]. We, therefore, propose in this study to optimize photodynamic therapy (PDT) conditions in vitro by simulating bacterial coinfection conditions in nasal cavities evaluated by the response surface method, where we can evaluate interactions of treatment variables. From this, the clinical case of the treatment of rhinosinusitis was carried out using PDT with nasal lighting. The absence of symptoms that characterize the disease was monitored and evaluated by the Kepler Meyer method. The study points out considerations that can be evaluated for the treatment to be a possibility of clinical indication in the control of rhinosinusitis., 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. Published by Elsevier B.V.)

Background: Analgesics are the most common form of managing low back pain (LBP). No previous study has examined which domains and intensities of physical activity are most beneficial in reducing the frequency of analgesic use for LBP and its related activity limitation., Methods: This cohort study forms part of the AUstralian Twin low BACK pain study, investigating the impact of physical activity on LBP. Information on demographics, LBP and health-related factors, including physical activity, were collected at baseline. Data on the total counts of analgesic use and activity limitation for LBP were collected weekly for one-year. Negative binomial regression models were conducted separately for each type of physical activity. Results were presented as incidence rate ratios (IRRs) and 95% confidence intervals (CIs)., Results: From an initial sample of 366 participants, 86 participants reported counts of analgesic use and 140 recorded counts of activity limitation across the follow-up period. The negative binomial regression models for analgesic use counts indicated that engagement in moderate-vigorous physical activity was protective for use of analgesics (IRR 0.97, 95% CI 0.96-0.99), while physical workload was associated with greater use (IRR 1.02, 95% CI 1.01-1.05). No other significant relationships were observed for the other measures of physical activity. For activity limitation counts, engagement in leisure activity was associated with less counts of activity limitation (IRR 0.94, 95% CI 0.81-0.99), while greater amounts of sedentary time was associated with higher counts (IRR 1.04, 95% CI 1.01-1.09). No other significant relationships were observed for the other measures of physical activity., Conclusions: Our findings highlight the potential importance of supporting engagement in moderate-vigorous and leisure physical activity as well as minimizing sedentary time and physical workload to reduce the risk of activity limitation and the need for analgesic use in people with LBP., Significance: We examined which domains and intensities of physical activity are most beneficial in reducing the frequency of analgesic use for low back pain and its related activity limitation. Engaging in moderate-vigorous and leisure physical activity as well as minimizing sedentary time and physical workload has the potential to reduce the risk of activity limitation and the need for analgesic use in people with low back pain., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Shape-switchable cyclophane hosts allow the controlled capture and release of reactive polypyridineRu(ii) complexes in water. This gives rise to a network of host-guest binding, acid-base reactions in ground and excited states, and chemical redox interconversions. In the case of (2-(2'-pyridyl)imidazole)Ru(ii) complexes, several molecular logic gate arrays of varying complexity emerge as a result. Cyclophane-induced 'off-on' switching of luminescence in neutral solution is found to originate from two features of these aromatic hosts: enhancement of radiative decay by the polarizable host and the suppression of nonradiative decay involving deprotonation by reducing the water content within the deep host cavity. These are examples of nanometric coordination chemistry/physics being controlled by inclusion in an open box. The aromatic units of the macrocycle are also responsible for the shape-switching mechanism of wall collapse/erection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hydrogels are a great ally in the pharmaceutical and biomedical areas. They have a three-dimensional polymeric structure that allows the swelling of aqueous fluids, acting as an absorbent, or encapsulating bioactive agents for controlled drug release. Interestingly, plants are a source of biogels, specifically polysaccharides, composed of sugar monomers. The crosslinking of these polymeric chains forms an architecture similar to the extracellular matrix, enhancing the biocompatibility of such materials. Moreover, the rich hydroxyl monomers promote a hydrophilic behavior for these plant-derived polysaccharide gels, enabling their biodegradability and antimicrobial effects. From an economic point of view, such biogels help the circular economy, as a green material can be obtained with a low cost of production. As regards the bio aspect, it is astonishingly attractive since the raw materials (polysaccharides from plants-cellulose, hemicelluloses, lignin, inulin, pectin, starch, guar, and cashew gums, etc.) might be produced sustainably. Such properties make viable the applications of these biogels in contact with the human body, especially incorporating drugs for controlled release. In this context, this review describes some sources of plant-derived polysaccharide gels, their biological function, main methods for extraction, remarkable applications, and properties in the health field.

Bees represent efficient bioindicators of environmental contamination, including elements that can accumulate in both biomes and bee-derived products. Therefore, the goal of this study was to evaluate the presence of metallic elements over the body surface of Melipona quadrifasciata anthidioides workers from rural and urban areas from Caatinga in Brazil. Using SEM/XEDS (scanning electron microscope/energy dispersive X-ray spectroscopy) identified magnesium (Mg), aluminum (Al), calcium (Ca), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), molybdenum (Mo), cadmium (Cd), barium (Ba), and lead (Pb) in the corbiculae of bees. The areas had similar profiles, but As was characterized as a "trace element" in the agricultural area and "minor element" in the urban area. The presence of toxic elements such as As, Cd, and Pb indicates that both areas may be contaminated, revealing the importance of metallic elements microanalysis in native bee species for environmental biomonitoring., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to evaluate the effect of regrowth ages and the use of powdered molasses on nutritional characteristics of Zuri grass (Megathyrsus maximus) silages. A completely randomized design was used, in a 3 × 3 factorial scheme: three regrowth ages (65, 80, and 95 days) and three inclusion levels of powdered molasses of sugarcane (0, 20, and 40 g), with four replications. The chemical composition, fermentation parameters, in vitro digestibility, and in vitro degradation kinetics of the silages were evaluated. Greater dry matter (DM) contents were observed in silages with 95 days with 40 g of molasses. The 65 days of regrowth silages with 40 g of molasses had greater in vitro digestibility of dry matter compared to other treatments. However, lower pH values, N-NH 3 , DM losses, gas losses, and density were observed in silages with 95 days of regrowth with 40 g of molasses. It is recommended to cut the Zuri grass in the range of 80 to 95 days of regrowth with the addition of 40 g/kg of molasses in powders for the production of silages., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Activated ghrelin receptor GHS-R1α triggers cell signalling pathways that modulate energy homeostasis and biosynthetic processes. However, the effects of ghrelin on mRNA translation are unknown. Using various reporter assays, here we demonstrate a rapid elevation of protein synthesis in cells within 15-30 min upon stimulation of GHS-R1α by ghrelin. We further show that ghrelin-induced activation of translation is mediated, at least in part, through the de-phosphorylation (de-suppression) of elongation factor 2 (eEF2). The levels of eEF2 phosphorylation at Thr56 decrease due to the reduced activity of eEF2 kinase, which is inhibited via Ser366 phosphorylation by rpS6 kinases. Being stress-susceptible, the ghrelin-mediated decrease in eEF2 phosphorylation can be abolished by glucose deprivation and mitochondrial uncoupling. We believe that the observed burst of translation benefits rapid restocking of neuropeptides, which are released upon GHS-R1α activation, and represents the most time- and energy-efficient way of prompt recharging the orexigenic neuronal circuitry., (© 2022. The Author(s).)

Soybean has a recognized narrow genetic base that often makes it difficult to visualize available genetic and phenotypic variability and identify superior genotypes during the selection process. However, the phenotypic expression of soybean plants is highly affected by photoperiod and the cultivation of a given variety is performed in the latitude range that presents ideal conditions for its development based on its relative maturity group (RMG) for the optimization of the phenotypic expression of its genotype. Based on the above, this study aimed to evaluate the efficiency of artificial neural networks (ANNs) as a tool for the correct discrimination and classification of tropical soybean genotypes according to their relative maturity group during the population selection process with the aim of optimizing the phenotypic performance of these selected genotypes. For this purpose, three biparental populations were synthesized, one with a wide genetic variability for the RMG character obtained from the hybridization between genitors of maturity groups RMG 5 (Sub-tropical 23° LS) × RMG 9.4 (Tropical 0° LS) and two populations with a narrow variability obtained between genitors RMG 7.3 (Tropical 20° LS) × RMG 9.4 and RMG 5.3 × RMG 6.7, respectively. Criteria for comparing the developed ANN architecture with Fisher's linear and Anderson's quadratic parametric discriminant methodologies were applied to the data for the discrimination and classification of the genotypes. ANN showed an apparent error rate of less than 8.16% as well as a low influence of environmental factors, correctly classifying the genotypes in the populations even in cases of reduced genetic variability such as in the RMG 5 × RMG 6 population. In contrast, the discriminant functions were inefficient in correctly classifying the genotypes in the populations with genealogical similarity (RMG 5 × RMG 6) and wide genetic variability, with an error rate of more than 50%. Based on the results of this study, ANN can be used for the discrimination of genotypes in the initial generations of selection in breeding programs for the development of high performance cultivars for wide and reduced photoperiod amplitudes, even with fewer selection environments, more efficiently, and with fewer time and resources applied. As a result of similarity between the parents, ANN can correctly classify genotypes from populations with a narrow genetic base, in addition to pure lines and genotypes with a high degree of inbreeding., 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 de Oliveira Amaral, Miranda, Val, Silva, Moitinho and Unêda-Trevisoli.)

Background: There is currently no clinically validated biomarker to predict respiratory compromise in sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold time (Ct), absolute lymphocyte count (AL) and neutrophil:lymphocyte ratio (NLR) have been previously evaluated for this purpose. We hypothesized that the combination of these parameters at presentation may be predictive of hypoxia (oxygen saturation <92%)., Methods: Data were collected on 118 patients with SARS-CoV-2 infection between May 2020 and April 2021. Demographics, clinical parameters and laboratory and radiological investigation results were recorded. Respiratory compromise (RC) was defined based on symptoms and signs, hypoxia and chest X-ray abnormalities., Results: RC occurred in 61 (51.7%) of patients. The Ct, AL and NLR at median day 3 of illness were significantly different between patients with and without RC (Ct, RC vs not: 19.46±2.64 vs 22.62±3.37, p=0.0001; AL, RC vs not: 531.49±289.09 vs 764.69±481.79, p=0.0001; NLR, RC vs not: 3.42±0.75 vs 2.59±0.55, p=0.0001). Receiver operating characteristics analysis showed that a Ct <19.9, AL <630.8×103/μL and NLR >3.12 at median day 3 of symptoms was predictive of hypoxia on day 7 of illness (area under the curve 0.805, sensitivity 96.7%, specificity 69.1%). The predictive value for the parameters combined was significantly superior to their individual predictive power., Conclusions: Ct, AL and NLR used in combination on day 3 of symptoms are predictive of hypoxia on day 7 of SARS-CoV-2 illness., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The aim with this study was to use interdisciplinary techniques and visions in order to identify the modulating effect of tannins on adaptive factors in lactating goats with different genetic patterns, through the assessment of digestibility and nutrient intake, ingestive behavior and rumen metagenome. We used in this study 8 of the Repartida ecotype and 6 of the Canindé breed goats, on average five years old, distributed in a completely randomized design, in a 2 × 2 factorial design, with two genetic groups and two diets. The applied diets were: basal diet and inclusion of 5% commercial tannin extract in basal diet. Intake and apparent digestibility of nutrients were evaluated, based on the quantification of the offered feed and refusals, and bromatological evaluation of samples of the offered feed, refusals and feces. Behavioral data were collected in 24-h continuous visual observations. The ruminal fluid was collected and DNA extraction, sequencing, and evaluation of relative abundance of the rumen microbiome were performed. The data obtained were analyzed statistically, through analysis of variance with 5% significance and, when necessary, a comparison of means test was applied. In this preliminary findings was observed that the genetic group factor caused changes in the number of chews and the relative abundance of microorganisms (P = 0.0290 and P = 0.0051). The diet factor influenced digestibility, which better values were observed for the tannin diet (P = 0.0049), in addition, it promoted changes in the rumen microbiota, with a beneficial modulatory characteristic. The inclusion of 5% tannin extract from Acacia mearnsii modulates the rumen microbiome, improving the apparent digestibility of nutrients without affecting the feed intake of goats from the Repartida and Canindé genetic groups., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Meloidogyne incognita is the most economically important species of the root-knot nematode complex causing damage to several crops worldwide. During parasitism in host plants, M. incognita secretes several effector proteins to suppress the plant immune system, manipulate the plant cell cycle, and promote parasitism. Several effector proteins have been identified, but their relationship with plant parasitism by M. incognita has not been fully confirmed. Herein, the Minc01696, Minc00344, and Minc00801 putative effector genes were evaluated to assess their importance during soybean and Nicotiana tabacum parasitism by M. incognita. For this study, we used in planta RNAi technology to overexpress dsRNA molecules capable of producing siRNAs that target and downregulate these nematode effector genes. Soybean composite roots and N. tabacum lines were successfully generated, and susceptibility level to M. incognita was evaluated. Consistently, both transgenic soybean roots and transgenic N. tabacum lines carrying the RNAi strategy showed reduced susceptibility to M. incognita. The number of galls per plant and the number of egg masses per plant were reduced by up to 85% in transgenic soybean roots, supported by the downregulation of effector genes in M. incognita during parasitism. Similarly, the number of galls per plant, the number of egg masses per plant, and the nematode reproduction factor were reduced by up to 83% in transgenic N. tabacum lines, which was also supported by the downregulation of the Minc00801 effector gene during parasitism. Therefore, our data indicate that all three effector genes can be a target in the development of new biotechnological tools based on the RNAi strategy in economically important crops for M. incognita control., (Copyright © 2022. Published by Elsevier Inc.)

Onychomycosis is the most common disease caused by fungal nail infections, and often caused by dermatophytes. This infection is very resistant to antifungal treatments, and promising Photodynamic Therapy (PDT) mediated treatments has been presented as a multitarget tracking. Optimization of PDT guide for uptake time, concentration of photosensitizers (PS) and the light dose to inactivate Trichophyton mentagrophytes. Curcumin derivatives, porphyrin Chlorin e6 (CHL-E6) and Chlorin-P6-6-N-butylamide-7-methyl-ester (CHL-butyl) were evaluated. PS photobleaching was observed on the hyphae photosensitized over the time, correlating the PS concentration and light dose of antifungal PDT. Porphyrin, Curcumin, Chl-e6 and Chl-butyl concentrations of 2.5 µg/mL, 0.025 µg/mL, 10 µg/mL and 5 µg/mL respectively, under illumination of 10.5 J/cm 2 were the best antifungal conditions found in the study. Curcumin, in low concentrations, and chlorin were the PSs with higher activity anti-T. mentagrophytes., (© 2022. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Fused filament fabrication (FFF) is the most popular additive manufacturing method, which allows the production of highly complex three-dimensional parts with minimal material waste. On the other hand, polyethylene terephthalate glycol (PETG) has been used to replace traditional polymers for 3D printing due to its chemical resistance and mechanical performance, among other benefits. However, when fibres are added, these PETG-based composites can be suitable for many different applications. Nevertheless, to guarantee their good performance in-service in these applications, and even extend to new ones, it is necessary for their mechanical properties to be maximized. Therefore, this study intends to optimize the printing parameters (nozzle temperature, printing speed, layer height and filling) in order to maximize the mechanical properties of printed PETG, PETG+CF (carbon fibre-reinforced PETG composites) and PETG+KF (aramid fibre-reinforced PETG composites). The Taguchi method was used for the experimental procedure design, and the specimens were produced according to the L16 orthogonal array. Finally, an analysis of variance (ANOVA) was performed, with a 95% confidence interval, to analyse the effect of the printing parameters on the bending properties. It was possible to conclude that the best bending properties for PETG, PETG+CF and PETG+KF were obtained for extrusion temperatures of 265 °C, 195 °C and 265 °C, printing speeds of 20, 60 and 20 mm/s, layer heights of 0.4, 0.53 and 0.35 mm and an infill density of 100% for the three materials, respectively.

The 2,4-dichlorophenoxyacetic acid (2,4-D) is an auxinic herbicide widely used in agriculture that is effective in controlling weeds. It is directly applied to the soil, to ponds or sprayed onto crops; thus, it can progressively accumulate in environmental compartments and affect non-target organisms. The aim of the present meta-analytic review is to investigate the toxic effects of 2,4-D, based on a compilation of results from different studies, which were synthesized to form a statistically reliable conclusion about the lethal effect of potentially ecological concentrations of 2,4-D in several animal species. The search was carried out in the Web of Science and Scopus databases. After the selection process was over, 87 datasets were generated and analyzed. The overall effect has indicated significant increase in the mortality rate recorded for animals exposed to environmental concentrations of 2,4-D compared to the control in the experiment (unexposed animals). The segregation of animals into taxonomic categories has shown that fish and birds presented higher mortality rates after exposure to the investigated substance. The present meta-analysis indicated larval and adult animals were susceptible among the ontogenetic development stages. Juvenile individuals exposed to different 2,4-D concentrations did not show significant difference in comparison to the control. Organisms exposed to 2,4-D immersion were the most impacted compared to those exposed by oral, spray and contact. Animals subjected to commercial formulation presented higher mortality rate than the analytical standard. Thus, 2,4-D can, in fact, increase mortality rate in animals, but it depends on species sensitivity, life stage and exposure route. This is the first meta-analytical study evaluating the mortality rate after 2,4-D exposure in several animal species., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Human behavior is crucial in health outcomes. Particularly, individual behavior is a determinant of the success of measures to overcome critical conditions, such as a pandemic. In addition to intrinsic public health challenges associated with COVID-19, in many countries, some individuals decided not to get vaccinated, streets were crowded, parties were happening, and businesses struggling to survive were partially open, despite lockdown or stay-at-home instructions. These behaviors contrast with the instructions for potential benefits associated with social distancing, use of masks, and vaccination to manage collective and individual risks., Objective: Considering that human behavior is a result of individuals' social and economic conditions, we investigated the social and working characteristics associated with reports of appropriate protective behavior in Brazil., Methods: We analyzed data from a large web survey of individuals reporting their behavior during the pandemic. We selected 3 common self-care measures: use of protective masks, distancing by at least 1 m when out of the house, and handwashing or use of alcohol, combined with assessment of the social context of respondents. We measured the frequency of the use of these self-protective measures. Using a frequent pattern-mining perspective, we generated association rules from a set of answers to questions that co-occur with at least a given frequency, identifying the pattern of characteristics of the groups divided according to protective behavior reports., Results: The rationale was to identify a pool of working and social characteristics that might have better adhesion to behaviors and self-care measures, showing these are more socially determined than previously thought. We identified common patterns of socioeconomic and working determinants of compliance with protective self-care measures. Data mining showed that social determinants might be important to shape behavior in different stages of the pandemic., Conclusions: Identification of context determinants might be helpful to identify unexpected facilitators and constraints to fully follow public policies. The context of diseases contributes to psychological and physical health outcomes, and context understanding might change the approach to a disease. Hidden social determinants might change protective behavior, and social determinants of protective behavior related to COVID-19 are related to work and economic conditions., Trial Registration: Not applicable., (©Gabriel Urbanin, Wagner Meira, Alexandre Serpa, Danielle de Souza Costa, Leonardo Baldaçara, Ana Paula da Silva, Rafaela Guatimosim, Anísio Mendes Lacerda, Eduardo Araújo Oliveira, Andre Braule, Marco Aurélio Romano-Silva, Antônio Geraldo da Silva, Leandro Malloy-Diniz, Gisele Pappa, Débora Marques Miranda. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 15.06.2022.)