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One of the proposed ways to reduce the climate impact of civil aviation is rerouting aircraft to minimise the formation of warming contrails. As this strategy may increase fuel consumption, it would only be beneficial if the climate impact reduction from the avoided contrails exceeds the negative impact of any additional carbon dioxide (CO2) emitted by the rerouted flight. In this study, we calculate the surface temperature response of almost half a million flights that crossed the North Atlantic sector in 2019 and compare it to the temperature response of hypothetical rerouted flights. The climate impacts of contrails and CO2 are assessed through the perspective of CO2-equivalence metrics, represented here as nine combinations of different definitions and time horizons. We estimate that the total emitted CO2 and the persistent contrails formed will have warmed the climate by 17.2 µK in 2039, 13.7 µK in 2069, and 14.1 µK in 2119. Under an idealised scenario where 1 % additional carbon dioxide is enough to reroute all contrail-forming flights and avoid contrail formation completely, total warming would decrease by 4.9 (−28 %), 2.6 (−19 %), and 1.9 (−13 %) µK in 2039, 2069, and 2119, respectively. In most rerouting cases, the results based on the nine different CO2-equivalence metrics agree that rerouting leads to a climate benefit, assuming that contrails are avoided as predicted. But the size of that benefit is very dependent on the choice of CO2-equivalence metrics, contrail efficacy and CO2 penalty. Sources of uncertainty not considered here could also heavily influence the perceived benefit. In about 10 % of rerouting cases, the climate damage resulting from contrail avoidance indicated by CO2-equivalence metrics integrated over a 100-year time horizon is not predicted by metrics integrated over a 20-year time horizon. This study highlights, using North Atlantic flights as a case study, the implications of the choice of CO2-equivalence metrics for contrail avoidance, but the choice of metric implies a focus on a specific climate objective, which is ultimately a political decision.

Abstract Background The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear. Methods We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure). Results 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008). Conclusions In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Relative humidity with respect to ice (RHi) is a key variable in the formation of cirrus clouds and contrails. We document its probability density function (PDF) using long-term Measurements of Ozone, Water Vapour, Carbon Monoxide and Nitrogen Oxides by In-Service Airbus Aircraft (MOZAIC) and the In-service Aircraft for a Global Observing System (IAGOS) observations over the period 1995–2022 in the upper troposphere (UT) and the lower stratosphere (LS) between 325 and 175 hPa. The characteristics of the RHi PDF differ in the UT and in the LS of the high-latitude regions (HLs) and mid-latitude regions (MLs) of the Northern Hemisphere. In the LS, this PDF decreases exponentially with increasing RHi. In the UT, it first increases exponentially in subsaturated conditions and then decreases exponentially in supersaturated conditions. Because of these different behaviors, the PDF for the combined UT and LS is bimodal. In contrast to the HLs and the MLs, the RHi PDF in the tropical troposphere decreases exponentially with increasing RHi. The different forms of PDF, in the tropics and in the higher-latitude regions, lead to a global PDF of RHi in subsaturated tropospheric conditions that is almost uniform. These findings invite caution when using MOZAIC and IAGOS measurements to calibrate large-scale simulations of RHi. The variability in RHi properties associated with that of temperature also has implications for the formation of contrails. We examined the impact of switching fuel (from kerosene to bioethanol or liquid hydrogen) on the frequency of contrail formation using the Schmidt–Appleman criterion. We show that bioethanol and, to a larger extent, liquid hydrogen would produce more contrails. The impact of a potential change from kerosene to these alternative fuels decreases with decreasing pressure but increases when moving from the higher latitudes of the Northern Hemisphere to the tropics. Finally, we emphasize that investigations of the impact on contrail occurrence frequency as a result of switching from fossil kerosene to more sustainable fuels must be carried out in various meteorological conditions.

Integrating knowledge regarding habitat characteristics and animal behaviour into conservation programs has the potential to impact the results of management and conservation efforts. This study aimed to explore the relationship between spatial and environmental data on the nesting activity of the European pond turtle, Emys orbicularis. Additionally, it sought to analyse the abundance, activity pattern, and behaviour of potential nest predators of E. orbicularis. Natural predated nests of the European pond turtle were utilized to characterise nesting habitat features, while artificial nests and camera traps were deployed to identify potential predators and their behaviour. Artificial nests and camera traps were established in areas with evidence of track detection or historical observations indicating past instances of nest predation. The nest site distribution of the European pond turtle showed a positive relationship with north-south oriented canals, the presence of vegetative components on embankments (shrubs, grass, emergent vegetation), finer-grained soil components (silt and clay), and soil moisture. Camera trapping of artificial nests revealed mammals (Meles meles and Vulpes vulpes) and a bird (Pica pica) as predators engaging in digging and destroying behaviour. P. pica detection was notably higher in mowed vegetation areas. Results indicate that natural nest distribution and predation on artificial nests may be influenced by their distribution concerning human-controlled vegetation and foraging activities of common nest predators. Protecting nesting sites in predator-frequented habitats, combined with landscape management targeting vegetation control along embankments, could mitigate nest predation and enhance hatchling recruitment.

Working Memory (WM) training has shown promise in supporting cognitive functioning in older adult populations, but effects that generalize beyond the trained task have been inconsistent. Targeting cognitive processes in isolation might be a limiting factor given that metacognitive and motivational factors have been shown to impact older adults engagement with challenging cognitive activities, such as WM training. The current feasibility study implemented a novel metacognitive intervention in conjunction with WM training in older adults and examined its potential amplifying short- and long-term effects on cognitive and self-report outcomes as compared to WM or active control training alone. One-hundred and nineteen older adults completed a cognitive training over the course of 20 sessions at home. The cognitive training targeted either WM or general knowledge. In addition, one of the WM training groups completed a metacognitive program via group seminars. We tested for group differences in WM, inhibitory control, and episodic memory, and we assessed participants perceived self-efficacy and everyday memory failures. At post-test, we replicated earlier work by demonstrating that participants who completed the WM intervention outperformed the active control group in non-trained WM measures, and to some extent, in inhibitory control. However, we found no evidence that the supplemental metacognitive program led to benefits over and above the WM intervention. Nonetheless, we conclude that our metacognitive program is a step in the right direction given the tentative long-term effects and participants positive feedback, but more longitudinal data with larger sample sizes are needed to confirm these early findings.

Abstract Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.

In this work pyrolysis of palm oil and lignin has been investigated using a two-stage process at 550 °C, with a first step configuration of continuous condensation for vapors and separation of gases, and a second step with distillation of vapors. Experiments were realized as pyrolysis of palm oil, palmitic acid, and Kraft lignin, as well as co-pyrolysis of palm oil/lignin, palmitic acid/lignin and palmitic acid/guaiacol. It has been shown that the addition of lignin improves the quality of palm oil pyrolysis bio-oil, thanks to the conversion of fatty acids coproduct to fatty acid methyl esters (FAME). The production of methyl esters in the reaction environment using palm oil and lignin was studied by conducting experiments with palmitic acid and lignin, as well as palmitic acid and guaiacol (the main product obtained from lignin pyrolysis). The results highlighted that during pyrolysis, the production of FAME is a consequence of a direct esterification reaction on palmitic acid. The formation of FAMEs during pyrolysis presents a promising avenue to optimize the utilization of palm oil by generating FAMEs as supplementary fuel products, Furthermore, it is possible to consider the application of the studied process for the conversion of free fatty acids into FAME.

Purpose: Wagner syndrome is an autosomal genetic vitreoretinopathy characterized by chorioretinal atrophy, avascular vitreous veils, reduced visual acuity and early retinal detachment in advanced cases. Management of Wagner syndrome usually results in observation then management of occurring complications. Observations: We report the case of a 9-year-old girl presenting with supposed Wagner syndrome that we managed with prophylactic encircling band and retinopexy in both eyes. The genetic testing revealed a new variant in the intron 7 non canonical splice acceptor site, c.4004-12_4004-6delins17, that was also present in her father. Conclusions and Importance: The VCAN variant found in this proband and her father has not been described yet but shows high predictions of pathogenicity. The previous reported variants in VCAN intron 7 and the associated phenotype for both cases allowed us to attribute this variant to Wagner syndrome. In Wagner syndrome, management is usually curative. After prophylactic surgery in our case, the zones of retinal delamination were well supported by the scleral buckle, releasing the vitreoretinal tractions, and the additional laser focalized on the temporal zones of dehiscence secured the retina. An encircling band may be a good way to prevent RD in patients with Wagner syndrome at risk.

Not available.

Abstract MEN1611 is a novel orally bioavailable PI3K inhibitor currently in clinical development for patients with HER2‐positive (HER2+) PI3KCA mutated advanced/metastatic breast cancer (BC) in combination with trastuzumab (TZB). In this work, a translational model‐based approach to determine the minimum target exposure of MEN1611 in combination with TZB was applied. First, pharmacokinetic (PK) models for MEN1611 and TZB in mice were developed. Then, in vivo tumor growth inhibition (TGI) data from seven combination studies in mice xenograft models representative of the human HER2+ BC non‐responsive to TZB (alterations of the PI3K/AkT/mTOR pathway) were analyzed using a PK‐pharmacodynamic (PD) TGI model for co‐administration of MEN1611 and TZB. The established PK‐PD relationship was used to quantify the minimum effective MEN1611 concentration, as a function of TZB concentration, needed for tumor eradication in xenograft mice. Finally, a range of minimum effective exposures for MEN1611 were extrapolated to patients with BC, considering the typical steady‐state TZB plasma levels in patients with BC following three alternative regimens (i.v. 4 mg/kg loading dose +2 mg/kg q1w, i.v. 8 mg/kg loading dose +6 mg/kg q3w or s.c. 600 mg q3w). A threshold of about 2000 ng·h/ml for MEN1611 exposure associated with a high likelihood of effective antitumor activity in a large majority of patients was identified for the 3‐weekly and the weekly i.v. schedule for TZB. A slightly lower exposure (i.e., 25% lower) was found for the 3‐weekly s.c. schedule. This important outcome confirmed the adequacy of the therapeutic dose administered in the ongoing phase 1b B‐PRECISE‐01 study in patients with HER2+ PI3KCA mutated advanced/metastatic BC.

Free-living amoebae (FLA) are amphizoic protozoans with a cosmopolitan distribution. Some strains of species are associated with infections in humans. They feed on microorganisms by phagocytosis; however, some of these can become endocytobionts by resisting this process and taking shelter inside the amoeba. The whole world is experiencing increasing shortage of water, and sewage is being reused, so the study of this environment is important in public health context. The objective of this work was to identify FLA present in sewage treatment plants in Porto Alegre, Brazil. About 1 L samples were collected from eight stations (raw and treated sewage) in January, February, July, and August 2022. The samples were sown in monoxenic culture, and the isolated amoebae were subjected to morphological and molecular identification. Polymerase chain reaction results indicated the presence of the genus Acanthamoeba in 100% of the samples. Gene sequencing showed the presence of Acanthamoeba lenticulata and Acanthamoeba polyphaga - T5 and T4 genotypes - respectively, which are related to pathogenicity. The environment where the sewage is released can be used in recreational activities, exposing individuals to potential interactions with these amoebae and their potential endocytobionts, which may pose risks to public health. HIGHLIGHTS Free-living amoebae were isolated for the first time in sewage treatment plants (STPs) in Brazil.; In the STPs of Porto Alegre, RS, Brazil, only the genus Acanthamoeba was isolated, and genotypes associated with pathogenicity (T4 and T5) were identified.; The Guaíba lake and the Gravataí river receive the city's sewage and, consequently, can disperse Acanthamoeba spp.; Further research on the prevalence and identification of free-living amoebae in sewage is still needed in Brazil.;

Abstract We provide here a procedure enabling light sheet fluorescence microscopy (LSFM) of entire human eyes after iDISCO + -based clearing (ClearEye) and immunolabeling. Demonstrated here in four eyes, post-processing of LSFM stacks enables three-dimensional (3D) navigation and customized display, including en face viewing of the fundus similarly to clinical imaging, with resolution of retinal capillaries. This method overcomes several limitations of traditional histology of the eyes. Tracing of spatially complex structures such as anterior ciliary vessels and Schlemm’s canal was achieved. We conclude that LSFM of immunolabeled human eyes after iDISCO + -based clearing is a powerful tool for 3D histology of large human ocular samples, including entire eyes, which will be useful in both anatomopathology and in research.

Legionella is the pathogen that causes Legionnaires’ disease, an increasingly prevalent and sometimes fatal disease worldwide. In 2021, 97% of cases in Europe were caused by Legionella pneumophila. We present a mathematical model that can be used by public health officials to assess the effectiveness and efficiency of different Legionella monitoring and control strategies to inform government requirements to prevent community-acquired Legionnaires’ disease in non-hospital buildings. This simulation model was built using comprehensive data from multiple scientific and field-based sources. It is a tool for estimating the relative economic and human costs of monitoring and control efforts targeting either L. pneumophila or Legionella species and was designed to analyze the potential application of each approach to specific building classes across Italy. The model results consistently showed that targeting L. pneumophila is not only sufficient but preferable in optimizing total cost (direct and economic) for similar human health benefits, even when stress-tested with extreme inputs. This cost–benefit analytical tool allows the user to run different real-life scenarios with a broad range of epidemiological and prevalence assumptions across different geographies in Italy. With appropriate modifications, this tool can be localized and applied to other countries, states, or provinces.

Penetrating trauma is usually divided into stab and gunshot wounds (GSW). When considering GSW, the initial assessment involves the identification of all the wounds, to understand the projectile's trajectory as well as to determine which anatomic structures might have been damaged [1]. Rarely, the projectile might not leave the victim's body and embolize to a different region through large blood vessels. Known as Missile Embolism (ME), this uncommon complication can compromise multiple body segments, resulting in severe injuries, whether it occurs through an artery or a vein, such as pulmonary embolism, cardiac-valve incompetence, limb-threatening ischemia, coronary infarct, and stroke [2,3]. This is a case report of an 18-year-old male patient who suffered a gunshot wound and was submitted to an exploratory laparotomy which identified a laceration of the inferior vena cava. Further exams concluded that the bullet was embolized to the right hepatic vein. ME treatment will depend mostly on the bullet's placement; if located in the left circulation or arterial vessels, retrieval is the preferred treatment. It can be executed through surgical exploration or endovascular procedure [3,4,8] Venous ME has several treatment options, including conservative management if the patient remains asymptomatic [3–7]. Cases of paradoxical embolization might be managed as arterial ME [3,4].

Abstract Background The threatening impact of conventional agriculture (CA) on soils could be due to the detrimental effects on soil microbial communities. Conversely, organic agriculture (OA) is envisaged as potentially enhancing helpful microbial communities and is proposed as environmentally sustainable. The soil microbiome influences soil health and quality, hence, it requires deeper investigation and understanding. In this study, applying 16S metabarcoding and qPCR techniques, we compared the microbial patterns of long-term organically and conventionally managed soils to explore their similarities and differences. Results Total DNA quantification showed an over 20-fold higher amount of DNA in OA soils (mean = 22.1 ± 3.92 μg g−1), compared to CA soils (mean = 0.95 ± 0.17 μg g−1). While 16S metabarcoding evidenced the absence of significant differences among communities of the two farming systems in terms of ecological indices, the qPCR analyses targeting functional genes reported a significantly higher abundance of all considered targets in OA sites spanning up to four-fold log increases. While OA and CA did not appear to affect overall bacterial diversity or evenness per se, qPCR-based functional analysis in OA showed a consistently higher abundance of all the salient microbial genes tested, when compared to CA, underlying a potentially beneficial impact on soil fertility and sustainability. Conclusions In essence, the sequencing-based analysis of absolute bacterial diversity could not differentiate the farming systems based on the amount of diversity but identified a unique set of taxa defining each. Hence, pairing this evaluation with the qPCR-based functional gene analyses can be a suitable approach to distinguish the exerted effects of CA or OA on soils. Graphical Abstract

ABSTRACT The objective of this study was to evaluate the clinical biochemistry behavior of Black-Tufted Marmosets (Callithrix penicillatta) submitted to blood collection without sedation and after general anesthesia with anesthetics isoflurane or sevoflurane. Blood collections were performed on (M1) day before anesthesia by physical restraint, and (M2) after anesthesia. There were four groups: Isoflurane (GI) and Sevoflurane (GS) using an anesthetic box. GIM: isoflurane induction with mask for a shorter period. Control group (GP): physical restraint in both moments. Plasma was separated and frozen to measure clinic biochemistry values. Urea was higher at M2 in groups GI and GP. AST was higher in M2 in GI, GS, and GP and only GI showed an increase in CK in M2. Glucose was higher in M1 in the GI, GS, and GP groups and fructosamine was higher in M2 in the GI. Stress caused by physical restraint can cause biochemical changes and these must be considered when interpreting the exams. Both the inhalational anesthetic isoflurane and sevoflurane did not cause clinically significant changes in clinical biochemistry results.

Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. CDK6-AS1 silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By CDK6-AS1 silencing in vitro, AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs. In vivo, the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high CDK6-AS1 levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover CDK6-AS1 as crucial in myeloid differentiation and mitochondrial mass regulation.

Background: Coronavirus disease-19 (COVID-19) has spread worldwide since December 2019 and was officially declared a pandemic in March 2020. Due to the rapid transmission and the high fatality rate, drastic emergency restrictions were issued, with a negative impact on routine clinical activities. In particular, in Italy, many authors have reported a reduction in the number of breast cancer diagnoses and critical problems in the management of patients who accessed the breast units during the dramatic first months of the pandemic. Our study aims to analyze the global impact of COVID-19 in the two years of the pandemic (2020–2021) on the surgical management of breast cancer by comparing them with the previous two years. Methods: In our retrospective study, we analyzed all cases of breast cancer diagnosed and surgically treated at the breast unit of “Città della Salute e della Scienza” in Turin, Italy, making a comparison between the 2018–2019 pre-pandemic period and the 2020–2021 pandemic period. Results: We included in our analysis 1331 breast cancer cases surgically treated from January 2018 to December 2021. A total of 726 patients were treated in the pre-pandemic years and 605 in the pandemic period (−121 cases, 9%). No significant differences were observed regarding diagnosis (screening vs. no screening) and timing between radiological diagnosis and surgery for both in situ and invasive tumors. There were no variations in the breast surgical approach (mastectomy vs. conservative surgery), while a reduction in axillary dissection compared to the sentinel lymph node in the pandemic period was observed (p-value < 0.001). Regarding the biological characteristics of breast cancers, we observed a greater number of grades 2–3 (p-value = 0.007), pT stage 3–4 breast cancer surgically treated without previous neoadjuvant chemotherapy (p-value = 0.03), and a reduction in luminal B tumors (p-value = 0.007). Conclusions: Overall, we report a limited reduction in surgical activity for breast cancer treatment considering the entire pandemic period (2020–2021). These results suggest a prompt resumption of surgical activity similar to the pre-pandemic period.

Apesar da grande gama de direitos sociais, econômicos e culturais assegurada no texto constitucional brasileiro, diversos deles ainda enfrentam um grave problema de eficácia. Assim, valendo-se do método hipotético-dedutivo, esse artigo procurou entender se os atuais limites de aplicabilidade dos direitos de segunda dimensão no Brasil podem ser reduzidos por meio da aplicação das correntes de justiça discutidas na obra de Michael J. Sandel. As conclusões indicaram que a política do bem comum, ideia de justiça construída por Sandel, apesar de apresentar incompletudes, pode ser uma nova via para tentar ampliar a eficácia dos direitos de segunda dimensão no país.

Introduction: To date, tissue biopsy represents the gold standard for characterizing non-small-cell lung cancer (NSCLC), however, the complex architecture of the disease has introduced the need for new investigative approaches, such as liquid biopsy. Indeed, DNA analyzed in liquid biopsy is much more representative of tumour heterogeneity.Materials and methods: We performed a meta-analysis of 17 selected papers, to attest to the diagnostic performance of liquid biopsy in identifying EGFR mutations in NSCLC.Results: In the overall studies, we found a sensitivity of 0.59, specificity of 0.96 and diagnostic odds ratio of 24,69. Since we noticed a high heterogeneity among different papers, we also performed the meta-analysis in separate subsets of papers, divided by 1) stage of disease, 2) experimental design and 3) method of mutation detection. Liquid biopsy has the highest sensitivity/specificity in high-stage tumours, and prospective studies are more reliable than retrospective ones in terms of sensitivity and specificity, both NGS and PCR-based techniques can be used to detect tumour DNA in liquid biopsy.Discussion: Overall, liquid biopsy has the potential to help the management of NSCLC, but at present the non-homogeneous literature data, lack of optimal detection methods, together with relatively high costs make its applicability in routine diagnostics still challenging.

Climatic changes are leading to an increased number of flooding year by year which impacts negatively the metabolism of roots and influences the shoot metabolism which leads to a decline in soybean productivity. This can be more drastic when it is cultivated in lowland soils. Our group hypothesized that tolerant sister-line plants have more capacity to cope with oxidative stress due to better management of energy use and dissipation on photosynthesis machinery during root-flooding and recovery conditions, while in sensitive soybean sister-line the impairment of the photosynthetic use and dissipation of energy lead to an unbalanced redox state response. For that, soybean seeds from the same parents, PELBR15- 7015C (flooding tolerant) and PELBR15-7060 (flooding sensitive) were sowed and cultivated in 500 L capacity plastic containers with lowland soil simulating the field management process. At the reproductive stage, the roots were subjected to flooding for 11 days, then drained to analyze reoxygenation (3 d) and recovery (10 d). Tolerant plants have a greater ability to manage root flooding conditions compared to sensitive ones. The ability includes efficient energy use and dissipation, which minimizes the production of reactive oxygen species (ROS) and subsequent cell damage. Conversely, in sensitive sister lines, impaired electron transport chains lead to increased ROS production and damage. Upon reoxygenation and recovery, the tolerant sister lines exhibit a faster metabolism turnover, allowing them to cope more effectively with the stress on leaves and roots. While both sister lines are capable of detoxifying ROS, the tolerant sister line's superior ability to manage energy use and dissipation allows for more stable and rapid control of oxidative stress.

Background: The diagnosis of antiphospholipid syndrome (APS) is challenging in Latin America (LAM). There is no standardization of its principal type of diagnosis testing: the lupus anticoagulant (LA) test. The advisory board, with experts from different Latin American countries, to try to establish a standardization and better outcomes true to the clinical condition of the APS, drew up a consensus with 8 main recommendations:(1) For the determination of the activated partial thromboplastin time (APTT) test, there is lots of products available in the diagnostic market. Therefore, clarifications on the composition of the product should always be consulted, so APTT can be evaluated with components sensitive to the presence of LA. (2) The proximity between prescribers and laboratories is important to mitigate the test time-response. When not possible, the volume of data produced by the LA test could be high, leading to difficulties in finding the valuable clinical data. The establishment of this communication channel should increase the effectiveness of the LA investigation. (3) Preanalytical and analytical factors, added to the heterogeneity of anti-lupus antibodies and their forms of interaction with phospholipid-associated proteins, are limiting factors for LA tests when detecting all LA. The physician must provide a detailed description of the request, along with medical advice after positive results. Also, the laboratory performing the exam must receive qualified information. The recommendation is a standardized questionnaire for anamnesis on the use of anticoagulants. (4) On the pre-analytical, a clear analysis requires joint evaluation of basic routine tests, as PT/APTT. The unanimous recommendation: on every lupus anticoagulant study request, PT/APTT should be performed to screen the analysis and complement the interpretation. (5) Recent guideline recommends the application of APTT with different concentrations of phospholipids as a 2nd methodology and the mixing test. This needs a careful interpretation: false negative should be a constant alert. (6) Costs of reagents and consumables for performing the tests (screening, mixing and confirmation) of the LA test are challenging. Each laboratory manages its need to expand LA research, including additional APTT test. A strong recommendation is to seek, with health insurers and government agencies, and to merge the trials for the LA research into a single set, the Lupus Anticoagulant Study, covering all the tests necessary for the diagnosis. (7) The assessment and identification of diseases such as APS is not simple and requires knowledge from prescribers for suspicion, evaluation, diagnosis, and monitoring. The strongest recommendation for LAM is the development of a cover sheet for LA results in a standardized, and clear sequence. (8) The study of LA requires familiarity with the terms that comprise its analysis, different ways of informing and/or referring to the same terms can cause doubts to prescribers. The elaboration of an official nomenclature for LA studies to understand the results uniformly in an intuitive and clear way of the mnemonic used must be done. The adhesion to those recommendations will propose a more assertive communication between laboratories and all medical areas, bringing better outcomes to the patients’ pathway.

Introdução: O Tempo de Protrombina (TP) é utilizado para monitoramento de pacientes em uso de VKA. O ensaio pode ser analisado através de 2 curvas de calibração: por atividade ou por INR. O monitoramento de VKA deve ser feito pela calibração do INR. Na América Latina, a curva destinada ao INR não costuma ser rotineira. Objetivo: Avaliar a concordância dos valores obtidos pelas 2 curvas. Assim, a comparabilidade entre as curvas permitirá inferir o impacto da liberação do parâmetro INR em uma curva não dedicada para esse fim, e também do uso de INR para pacientes que não estão em terapia com VKA. Materiais e métodos: 138 amostras foram fornecidas pelo HU-USP. O equipamento utilizado foi o Sysmex®CS-2500 e os reagentes do TP foram Thromborel®S (THS) e Dade®Innovin® (INN). A análise dos resultados foi realizada a partir de gráficos do Microsoft Excel e do EP Evaluator. Resultados: A comparação entre as metodologias de obtenção do valor de INR mantendo o mesmo reagente demonstrou ótima correlação (THS R2 = 0,999; INN R2 = 0,997). Essa boa correlação também se manteve para valores de atividade (THS R2 = 0,9933, INN R2 = 0,9962). Quando manteve-se a mesma metodologia de obtenção dos valores de INR, mas comparando os 2 reagentes, a correlação foi mais fraca. INR calculado R2 = 0,9893. INR calibrado R2 = 0,9883. Atividade calculada R2 = 0,9204. Atividade calibrada R2 = 0,9222. Discussão: Os valores de INR̃1 quase não sofrem alteração, independente de como o valor de INR é obtido. Quando os valores de INR estão acima de 2, há maior variabilidade entre eles, mas ainda sem diferença clínica. Mantendo-se o tipo de cálculo de INR e mudando-se o reagente, a correlação não se apresenta forte. Observa-se que a maioria dos pontos com INR normal̃ 1,0 está dentro do TEa, mas que, conforme o valor de INR aumenta, os valores dispersam mais da linha de regressão. A situação se repete com INR calibrado e os 2 reagentes. Quando a correlação de atividade é estabelecida é possível inferir que a utilização de um métodos de obtenção não apresenta interferência clínica. Tanto para o valor de atividade obtido através de cálculo quanto calibração, os valores das amostras ultrapassaram o TEa. Essa observação pode interferir na clínica do paciente, já que os resultados não podem ser relacionáveis em sua totalidade, em especial para valores mais altos de atividade. Conclusão: Comparando-se as duas calibrações do mesmo reagente, nas amostras avaliadas as variações de valores foram irrelevantes. Quando analisa-se entre os 2 reagentes, há diferenças importantes para INR entre as calibrações. Em INR próximos a 1, a variação é mínima; porém a diferença cresce proporcionalmente aos valores de INR, logo os reagentes não são intercambiáveis. Isso endossa a literatura de que a terapia de VKA deve ser avaliada por TP com calibração INR. Para atividade, os dados mostram que para o mesmo reagente, com os valores ou calculados ou calibrados, a alteração é mínima em se tratando de amostras de valores normais. É possível inferir que os resultados são intercambiáveis para todos os valores de atividade.

BackgroundThe aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).MethodsAn open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.ResultsBetween the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm–time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = −6.7 cells/mm3; 95% CI; −16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.ConclusionNo evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT04054089.

Bamboo is already a convenient construction resource, as it offers an efficient structural performance. As this plant has native varieties adapted to different climates and soils of Brazil, bamboo silviculture can be intensified to supply the national industry. Three bamboo species from Brazil (Dendrocalamus asper, Bambusa tuldoides, and Phyllostachys aurea) were analyzed for the flexural load capacity applied on the internal and external surfaces. Specimens were prepared without knots and with knots centered at the middle of each sample. In total, 240 samples were tested in terms of static bending and dynamic bending (impact). The results showed a higher flexural elasticity and a higher proportional limit strength of knotted P. aurea. The presence of knots provided higher values of ultimate strength in P. aurea, even reducing the bamboo flexibility. Also, P. aurea exhibited the best characteristic of flexural dynamic energy absorption among the three bamboo species under evaluation.

Soil water infiltration is an important component of the hydrological cycle, and it is best evaluated when the raindrop impacts the ground surface. For this reason, it is affected by changes in land use and land cover and by the characteristics and physical–hydric properties of the soil. This study aimed to evaluate soil water infiltration in areas occupied by annual crops (soybean and corn) and pastures in two watersheds of the Teles Pires River-MT, using simulated rainfall, physical models, and principal component analysis. Infiltration rates were evaluated based on simulated rainfall with an average intensity of 75 mm h−1, with four repetitions per region (upper, middle, and lower) of the hydrographic sub-basins of the Caiabi and Renato rivers, and soil use with cover, without cover, and disturbed. Soil tillage provided higher water infiltration rates into the soil, especially in pasture areas in the two hydrographic sub-basins. There were significant adjustments to the mathematical models based on the infiltration rate data for all land use and land cover conditions. The soil attributes that most interfered with the infiltration rate were microporosity, bulk density, and total porosity in the crop areas of the middle Caiabi and microporosity, clay content, total porosity, and silt content in the areas farming at the source of the Renato River. The Horton and Philip models presented the best adjustments in the hydrographic sub-basins of the Caiabi and Renato Rivers, which are recommended for estimating the water infiltration rate into the soil in different uses, coverages, and regions.

Chilling temperatures represent a challenge for crop species originating from warm geographical areas. In this situation, biostimulants serve as an eco-friendly resource to mitigate cold stress in crops. Tomato (Solanum lycopersicum L.) is an economically important vegetable crop, but quite sensitive to cold stress, which it encounters in both open field and greenhouse settings. In this study, the biostimulant effect of a brown-seaweed extract (BSE) has been evaluated in tomato exposed to low temperature. To assess the product effects, physiological and molecular characterizations were conducted. Under cold stress conditions, stomatal conductance, net photosynthesis, and yield were significantly (p ≤ 0.05) higher in BSE-treated plants compared to the untreated ones. A global transcriptomic survey after BSE application revealed the impact of the BSE treatment on genes leading to key responses to cold stress. This was highlighted by the significantly enriched GO categories relative to proline (GO:0006560), flavonoids (GO:0009812, GO:0009813), and chlorophyll (GO:0015994). Molecular data were integrated by biochemical analysis showing that the BSE treatment causes greater proline, polyphenols, flavonoids, tannins, and carotenoids contents.The study highlighted the role of antioxidant molecules to enhance tomato tolerance to low temperature mediated by BSE-based biostimulant.

Abstract Background Loneliness is a major health issue among older adults. The aim of this study was to assess the relationship between loneliness, in its social and emotional facets, and the cognitive (language), and behavioral/psychological functioning as well as quality of life (QoL) in people with mild and moderate dementia, i.e., considering dementia severity as an individual characteristic. Methods This cross-sectional study involved 58 people with mild dementia and 55 people with moderate dementia. Participants completed the Social and Emotional Loneliness scale, along with measures assessing their language skills, the frequency and severity of their behavioral and psychological symptoms, and their QoL. Results Socio-demographic characteristics and depression, but not loneliness or its social and emotional facets, contributed to explain participants’ behavioral and psychological symptoms, regardless of dementia severity. Loneliness explained, though to a small extent (8% of variance), language skills in people with moderate dementia, with social loneliness only accounting for language skills (18% of variance) in this group. Loneliness also modestly accounted for dysphoria symptoms in both the mildly and moderately impaired (6% and 5% of variance, respectively) individuals with social loneliness predicting dysphoric mood in the former group only (7% of variance). Loneliness also explained, to a larger extent, QoL in both the mildly impaired and moderately impaired individuals (27% and 20% of variance, respectively), its social facet predicting QoL in the mildly impaired (30% of variance), and its emotional facet in the moderately impaired (21% of variance) group. Conclusion These findings suggest that loneliness and its facets have a clear impact on perceived QoL, and influence the language skills and dysphoria symptoms of people with dementia, to a degree that depends on dementia severity. The assessment of loneliness and its facets in people with dementia considering dementia severity, and the promotion of social inclusion to reduce it should be considered by professionals.

Oil palm (Elaeis guineensis Jacq.) is one of the agricultural crops with the greatest potential for vegetable oil production in Brazil. However, a disease of unknown etiology popularly known as Fatal Yellowin (FY) has caused damage to Brazilian farmers particularly in the eastern region of the Amazon. So, the objective of this study was to evaluate the spatial dependence of FY on three oil palm genotypes, grown for many years in an organic production system in the Amazon region. The study area had 4104 ha, divided into 139 plots. In each plot, the monthly incidence of disease was monitored forming a database. The number of diseased plants per year, number of accumulated diseased plants, number of diseased plants per hectare, growth rate of diseased plants and incidence of accumulated disease were evaluated. The results indicated spatial distribution of the variables adjusted to the gaussian, spherical and exponential models, with predominance of the first model. This increases the purpose that FY is caused by biotic factors. The highest range achieved in the study was 2929 m indicating the susceptibility of the tested genotypes. Some plots close to the river had the highest incidence of the disease on the study, probably associated with higher soil moisture.

IntroductionOne of various non-pharmacological treatments for people with dementia (PwD) is horticultural therapy. The aim of this double-blind, pre- and post-test, pilot study was to examine the effects of horticultural activities (HA) for PwD at a residential and daytime care facility. Whether combining HA with elements drawn from other psychosocial interventions (cognitive stimulation) would maximize any benefits was also newly examined.Materials and methodsTwenty-four PwD were involved either in HA, alone (TG1, N = 7) or combined with some cognitive stimulation (TG2, N = 8), or in indoor treatment-as-usual activities (CG, N = 9). Benefits were assessed in terms of general cognitive functioning (for participants with mild-to-moderate dementia), mood, behavioral and psychological symptoms, and quality of life.ResultsNo differences emerged between TG1 and TG2 in any outcome measure, so the two groups were combined (N = 15). Compared with the CG, the TG involved in HA exhibited less frequent and severe behavioral and psychological symptoms and an improved mood after the intervention. Caregivers also reported less distress in the TG after the intervention than in the CG. Considering only PwD with mild-to-moderate dementia, the TG also showed benefits in a measure of general cognitive functioning, and self-reported quality of life, compared with the CG.DiscussionOur results further confirm that engaging PwD in participatory HA in contact with natural elements can decrease their dementia symptoms and their caregivers’ distress, but also increase PwD’s quality of life. Our findings also suggest the need to consider dementia severity when assessing the benefits of horticultural therapy.

BackgroundIn triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available.MethodsWe carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years.ResultsOverall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles.ConclusionThe CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research.

IntroductionExposure to nature is known to support psychological wellbeing, and can support People with Dementia (PwD). Here we describe a case study conducted at a care facility for PwD to examine the effect of their exposure to nature after intervention to renovate an existing Therapeutic Garden (TG). Changes in frequency of attendance and behavior in the TG were examined. A single case was also considered to assess individual benefits.Materials and methodsTwenty-one PwD participated in the study. Their behavior in the TG was observed for 4 weeks before and after the intervention (using behavioral mapping), and measures of individual characteristics (general cognitive functioning, behavioral/neuropsychiatric symptoms, depression, and quality of life) were administered.ResultsTen of the 21 PwD visited the TG more often after the intervention, their social behaviors (e.g., talking to others) increased, and their active isolated behavior in the garden (e.g., smelling, touching flowers) tended to increase. The increase in social behavior related to less severe baseline depressive symptoms. Passive isolated behaviors related to more impaired baseline cognitive functioning. The case of Mrs. A extended the findings for the whole sample: although her dementia symptoms (apathy, motor disturbances) worsened, she visited the TG more often after the intervention, her social exchanges and active isolated actions increased, and her agitation and wandering decreased.DiscussionThese results support the benefits of exposure to nature for PwD, and underscore the importance of considering users’ profiles to optimize their use of a TG.

IntroductionA growing number of evidences suggest that the combination of hyperinflammation, dysregulated T and B cell response and cytokine storm play a major role in the immunopathogenesis of severe COVID-19. IL-6 is one of the main pro-inflammatory cytokines and its levels are increased during SARS-CoV-2 infection. Several observational and randomized studies demonstrated that tocilizumab, an IL-6R blocker, improves survival in critically ill patients both in infectious disease and intensive care units. However, despite transforming the treatment options for COVID-19, IL-6R inhibition is still ineffective in a fraction of patients.MethodsIn the present study, we investigated the impact of two doses of tocilizumab in patients with severe COVID-19 who responded or not to the treatment by analyzing a panel of cytokines, chemokines and other soluble factors, along with the composition of peripheral immune cells, paying a particular attention to T and B lymphocytes.ResultsWe observed that, in comparison with non-responders, those who responded to tocilizumab had different levels of several cytokines and different T and B cells proportions before starting therapy. Moreover, in these patients, tocilizumab was further able to modify the landscape of the aforementioned soluble molecules and cellular markers.ConclusionsWe found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis.

Background: The management of early breast cancer (BC) needs supervision and skill maintenance, and should be performed by specialists working as a team in multidisciplinary breast units. This approach aims to improve the long-term survival and quality of life of patients with BC. Methods: This was a prospective observational study including patients newly diagnosed with operable BC. The study encompassed the pre-surgical phase, throughout the diagnostic and surgical workout, and included post-therapeutic master multidisciplinary team meetings (MTMs) sessions, between 2019 and 2022. Results: We enrolled 280 patients with BC from eight breast units. The Senonetwork indicators regarding diagnosis, waiting time, loco-regional treatment, and adjuvant therapy were collected for each patient discussed. Conclusions: Overall, the majority of quality indicators were respected among breast units. The most critical issue referred to timing indicators: more than 30 days from MTM to surgery, more than 42 days from diagnosis to surgery, and more than 60 days from the first screening mammogram to surgery for many patients. Some aspects of the histopathological diagnosis of intraductal BC also need to be improved. Furthermore, other critical issues in our study regarded some aesthetical indicators, demonstrating low interest in these essential quality indicators.

Background and aims: It is well established that caloric restriction (CR) may influence metabolic and hormonal factors involved in cancer development and progression. Recently, several studies have demonstrated that CR may have a favorable impact on the response to systemic therapy in breast cancer (BC) patients. However, there is a lack of data regarding the influence of CR during neoadjuvant chemotherapy (NACT). Our study’s primary aim was to evaluate CR’s impact on BC patients undergoing NACT. Secondly, we investigated the nutritional efficacy and safety of this intervention. Methods: We performed a prospective, case–control study in two breast units. A diet group consisting of 39 patients undergoing NACT and CR was enrolled in our study at the same time. CR consisted of a 30% reduction in caloric intake, which increased to 50% on the days before, during, and after the administration of chemotherapy. A control group of 60 patients that underwent the same treatment approach only followed the general dietary recommendations for BC according to WCRF guidelines. The diet group was monitored during the study for both dietary adequacy and weight trends. Results: CR combined with NACT showed a statistically significant therapeutic response in tumor size (OR 2.94, IC 1.07–8.01, p = 0.009) and lymph node status (OR 3.22, IC 1.22–8.56, p = 0.001) compared to NACT alone, even after the adjustment for all biological parameters. Our data also showed the efficacy and safety of this intervention in both anthropometric and biochemical analyses. Conclusions: Patients who adhered to CR showed a better response to NACT, both in the breast and in the axillary lymph nodes, compared to the patients in the control group. Furthermore, the CR diet combined with NACT showed good tolerance and safety.