Enhancing Cellulose and Lignin Fractionation from Acacia Wood: Optimized Parameters Using a Deep Eutectic Solvent System and Solvent Recovery.

Cellulose and lignin, sourced from biomass, hold potential for innovative bioprocesses and biomaterials. However, traditional fractionation and purification methods often rely on harmful chemicals and high temperatures, making these processes both hazardous and costly. This study introduces a sustainable approach for fractionating acacia wood, focusing on both cellulose and lignin extraction using a deep eutectic solvent (DES) composed of choline chloride (ChCl) and levulinic acid (LA). A design of experiment was employed for the optimization of the most relevant fractionation parameters: time and temperature. In the case of the lignin, both parameters were found to be significant variables in the fractionation process (p-values of 0.0128 and 0.0319 for time and temperature, respectively), with a positive influence. Likewise, in the cellulose case, time and temperature also demonstrated a positive effect, with p-values of 0.0103 and 0.028, respectively. An optimization study was finally conducted to determine the maximum fractionation yield of lignin and cellulose. The optimized conditions were found to be 15% (w/v) of the wood sample in 1:3 ChCl:LA under a treatment temperature of 160 °C for 8 h. The developed method was validated through repeatability and intermediate precision studies, which yielded a coefficient of variation lower than 5%. The recovery and reuse of DES were successfully evaluated, revealing remarkable fractionation yields even after five cycles. This work demonstrates the feasibility of selectively extracting lignin and cellulose from woody biomass using a sustainable solvent, thus paving the way for valorization of invasive species biomass.

Four-Strata Risk Assessment in Patients with Pulmonary Arterial Hypertension Treated with Selexipag in Real-World Settings (EXPOSURE Study).

INTRODUCTION: Risk assessment can aid management of pulmonary arterial hypertension (PAH) and clinical decision-making. This analysis describes characteristics, treatment patterns and outcomes of patients with PAH, categorised by risk status at time of treatment escalation with selexipag in clinical settings. METHODS: Patients initiating selexipag in the ongoing multicentre, prospective EXPOSURE (EUPAS19085) study were grouped as low, intermediate-low, intermediate-high or high risk of 1-year mortality according to the ESC/ERS 4-strata method. RESULTS: As of November 2022, 77% (535/698) of patients initiating selexipag had data allowing for risk calculation; 14% (N = 76) were low, 31% (N = 168) intermediate-low, 34% (N = 182) intermediate-high and 20% (N = 109) high risk of 1-year mortality. Overall, patients were predominantly female (71%), with idiopathic/heritable PAH (56%) or PAH associated with connective tissue disease (CTD-PAH; 27%), median age of 60 years and prevalent (2 years) disease. From low to high risk, proportion of CTD-PAH and age increased (from 12%-40% and 46-68 years, respectively); time from diagnosis decreased and presence of cardiovascular risk factors increased. Most patients across risk groups (74-81%) initiated selexipag as part of triple oral combination therapy. Overall median (Q1, Q3) selexipag exposure duration was 10.1 (3.5, 24.1) months. Proportions of hospitalised patients increased with increasing risk group (16-42% from low to high, respectively); more hospitalisations were PAH-related for the high risk (71%) versus other risk groups (47-54%). Kaplan-Meier survival estimates were 98%, 98%, 93% and 80% at 1-year and 98%, 92%, 81% and 67% at 2-years, from low to high risk, respectively. CONCLUSIONS: In clinical settings, selexipag is initiated across all risk groups, predominantly as triple therapy. Only 45% of patients being at low/intermediate-low risk at selexipag initiation suggests an opportunity for more frequent patient monitoring and earlier treatment escalation, given that 4-strata risk assessment was prognostic for hospitalisations and survival in this contemporary PAH cohort. A graphical abstract is available with this article.

Pulmonary arterial hypertension (PAH) is a disease that gets worse over time. To make decisions about treatment, we need to know the stage of the disease. We can do this by measuring the patient's risk of death during the next few years. Selexipag is a medication for PAH. This analysis included patients living in Europe and Canada who started treatment with selexipag for their PAH disease. Our findings suggest that the monitoring of patients' health and the timing of starting selexipag can be improved. This analysis includes 698 patients taking part in the EXPOSURE study (EUPAS19085), which looks at the real-life treatment of patients with PAH. Overall, 71% of patients were female, the median age was 60 years, most had been diagnosed with PAH for around 2 years and were already taking two other medications for their PAH disease. At the beginning of selexipag treatment, 14% of patients were classified as low risk, 31% as intermediate-low risk, 34% as intermediate-high risk and 20% as high risk of mortality within the next year. More high-risk patients were hospitalised compared with the lower risk groups. After 1 year of treatment, more patients in the low (98%) and intermediate-low groups (98%) were alive than those in the intermediate-high (93%) and high risk groups (80%). The same was true after 2 years of treatment with selexipag (98%, 92%, 81% and 67%, respectively). This study confirms that assessing patients' risk levels can indicate how well they will do over time and shows that earlier treatment with selexipag should be considered to potentially prevent worsening of the disease.

Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag-treated PAH-CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH-CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety-eight selexipag-treated patients had follow-up information; 178 (26%) had PAH-CTD. The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years. There were 5% patients at low, 25% intermediate-low, 40% intermediate-high, and 30% high risk of 1-year mortality, according to the ESC/ERS 4-strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post-baseline. Over a median (Q1-Q3) selexipag exposure period of 8.6 (2.5-17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH-related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH-CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH-CTD by moving from escalating after years in response to clinical deterioration to escalating sooner to prevent clinical deterioration.

A synchronized, large-scale field experiment using Arabidopsis thaliana reveals the significance of the UV-B photoreceptor UVR8 under natural conditions.

This study determines the functional role of the plant ultraviolet-B radiation (UV-B) photoreceptor, UV RESISTANCE LOCUS 8 (UVR8) under natural conditions using a large-scale 'synchronized-genetic-perturbation-field-experiment'. Laboratory experiments have demonstrated a role for UVR8 in UV-B responses but do not reflect the complexity of outdoor conditions where 'genotype × environment' interactions can mask laboratory-observed responses. Arabidopsis thaliana knockout mutant, uvr8-7, and the corresponding Wassilewskija wild type, were sown outdoors on the same date at 21 locations across Europe, ranging from 39°N to 67°N latitude. Growth and climatic data were monitored until bolting. At the onset of bolting, rosette size, dry weight, and phenolics and glucosinolates were quantified. The uvr8-7 mutant developed a larger rosette and contained less kaempferol glycosides, quercetin glycosides and hydroxycinnamic acid derivatives than the wild type across all locations, demonstrating a role for UVR8 under field conditions. UV effects on rosette size and kaempferol glycoside content were UVR8 dependent, but independent of latitude. In contrast, differences between wild type and uvr8-7 in total quercetin glycosides, and the quercetin-to-kaempferol ratio decreased with increasing latitude, that is, a more variable UV response. Thus, the large-scale synchronized approach applied demonstrates a location-dependent functional role of UVR8 under natural conditions.

Early Mobilization Decision after an Acute Ischemic Stroke: Protocol for an Umbrella Review.

INTRODUCTION: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes. METHODS AND ANALYSIS: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494.

Quantitative assessment of carotid ultrasound diameter measurements in the operating room: a comparable analysis of long-axis versus rotated and tilted orientation.

Objective. Carotid ultrasound (US) has been studied as a non-invasive alternative for hemodynamic monitoring. A long-axis (LA) view is traditionally employed but is difficult to maintain and operator experience may impact the diameter estimates, making it unsuitable for monitoring. Preliminary results show that a new, i.e. rotated and tilted (RT) view is more robust to motion and less operator-dependent. This study aimed to quantitatively assess common carotid diameter estimates obtained in a clinical setting from an RT view and compare those to corresponding estimates obtained using other views.Approach. Carotid US measurements were performed in 30 adult cardiac-surgery patients (26 males, 4 females) with short-axis (SA), LA, and RT probe orientations, the first being used as a reference for measuring the true vessel diameter. Per 30 s acquisition, the median and spread in diameter values were computed, the latter representing a measure of robustness, and were statistically compared between views.Main results. The median (IQR) over all the patients of the median diameter per 30 s acquisition was 7.15 (1.15) mm for the SA view, 7.03 (1.51) mm for the LA view, and 6.99 (1.72) mm for the RT view. The median spread in diameter values was 0.18 mm for the SA view, 0.16 mm for the LA view, and 0.18 mm for the RT view. There were no statistically significant differences between views in the median diameter values (p= 0.088) or spread (p= 0.122).Significance. The RT view results in comparable and equally robust median carotid diameter values compared to the reference. These findings open the path for future studies investigating the use of the RT view in new applications, such as in wearable ultrasound devices.

Natalizumab extended interval dosing: what about wearing-off effect?

BACKGROUND: Up to two thirds of patients with multiple sclerosis (MS) under natalizumab report a resurgence of symptoms at the end of the natalizumab cycle (wearing-off (WO) effect). At the outbreak of COVID-19, in line with the international recommendations for MS management, our centre switched all clinically stable patients on natalizumab therapy for more than one year from standard interval dosing (SID) to extended interval dosing (EID) with every six weeks infusions. This study aimed to evaluate the impact of EID in WO in MS patients under natalizumab. METHODS: An observational retrospective study in patients with MS under natalizumab on EID was conducted. A questionnaire regarding current (on EID) and past (on SID) experience of WO effect was applied. RESULTS: Seventy-six patients were included. No significant differences were found in the annual relapse rate after the switch to EID (p = 0.083). However, there was a significant increase in the proportion of patients complaining of WO from 38.2% to 56.6% (p = 0.001). Moreover, patients with WO on SID, referred a significant increase in severity (p = 0.019) and duration of WO symptoms (p = 0.029), due to an anticipation of the symptoms relative to the day of natalizumab infusion (p = 0.019), when switching to EID. Symptoms improved with treatment maintenance in 23.3% of patients; instead, a reduction in interval dosing was needed in 54.8% with symptom improvement. CONCLUSION: WO affects a significant proportion of MS patients under natalizumab. Its prevalence, severity, and duration increase on EID, therefore despite clinical effectiveness maintenance of this posology should be individualized.

Real-World Management of Patients with Pulmonary Arterial Hypertension: Insights from EXPOSURE.

INTRODUCTION: Further insights into real-world management and outcomes of patients with pulmonary arterial hypertension (PAH) are needed. This interim analysis of the ongoing, multicentre, prospective EXPOSURE (EUPAS19085) observational study describes characteristics, treatment patterns and outcomes of patients with PAH initiating a new PAH-specific therapy in Europe/Canada. METHODS AND RESULTS: All analyses were descriptive. In total, 1944 patients with follow-up information were included; the majority were female, with World Health Organization functional class II/III symptoms and with idiopathic PAH or connective tissue disease-associated PAH. Most incident patients (N = 1100; diagnosed for ≤ 6 months) initiated treatment as monotherapy (48%) or double therapy (43%). Of those initiating monotherapy, 38% (199/530) escalated to double therapy (median [Q1, Q3] time to escalation 3.4 [1.9, 6.6] months), and of those initiating double therapy, 17% (78/457) escalated to triple therapy (median [Q1, Q3] time to escalation 7.0 [3.4, 12.7] months) during the observation period (median [Q1, Q3]: 17.0 [7.5, 29.9] months). The majority of the 834 prevalent patients (diagnosed > 6 months) entered the study on initiation of combination therapy and most did not change treatment regimen during the observation period (median [Q1, Q3]: 19.6 [10.2, 32.2] months). One-year survival was 88% for incident patients and 90% for prevalent patients. CONCLUSIONS: Results from EXPOSURE suggest a shift towards combination therapy and the alignment of real-world treatment patterns with current guideline recommendations. While survival estimates are encouraging, the extent of monotherapy use at treatment initiation and follow-up highlight an opportunity for further improvements through optimisation of treatment strategies in line with current guidelines. A graphical abstract is also available with this article. TRIAL REGISTRATION NUMBER: EUPAS19085.

Pulmonary arterial hypertension (PAH) is a progressive disease. Clinical guidelines recommend that most patients start treatment with a combination of different PAH medications. While there is no cure for PAH, these medications help to control symptoms and slow disease worsening. To understand treatments currently used in clinical practice, we analysed data from EXPOSURE (EUPAS19085), an ongoing study collecting information from patients starting a new PAH medication in Europe and Canada. Most patients in the study were female, with World Health Organization functional class II/III symptoms, and idiopathic (unknown cause) PAH or PAH associated with connective tissue disorders. Among 1100 patients who were 'recently diagnosed' (diagnosed with PAH in the past 6 months), 88% were alive after 1 year. We found that 48% started treatment with one PAH medication, and 38% of those patients had a second medication prescribed within a median period of 3 months. Among the 457 'recently diagnosed' patients treated with two PAH medications when they entered the study, 17% had a third medication prescribed within a median period of 7 months. Among 834 patients with 'established PAH' (diagnosed more than 6 months ago), 90% were alive after 1 year. Most entered the study when they started a third medication and did not have further changes in treatment. Our findings show that patients with PAH are often treated with one medication in clinical practice as well as a combination of medications. While survival rates are encouraging, the extent to which one PAH medication is used suggests there is room for treatment improvement.

Novel HER-2 Targeted Therapies in Breast Cancer.

Human epidermal growth factor 2 (HER-2)-positive breast cancer represents 15-20% of all breast cancer subtypes and has an aggressive biological behavior with worse prognosis. The development of HER-2-targeted therapies has changed the disease's course, having a direct impact on survival rates and quality of life. Drug development of HER-2-targeting therapies is a prolific field, with numerous new therapeutic strategies showing survival benefits and gaining regulatory approval in recent years. Furthermore, the acknowledgement of the survival impact of HER-2-directed therapies on HER-2-low breast cancer has contributed even more to advances in the field. The present review aims to summarize the newly approved therapeutic strategies for HER-2-positive breast cancer and review the new and exploratory HER-2-targeted therapies currently under development.

Influence of dietary pattern on anti-tuberculosis treatment outcomes in persons with dysglycemia: a Peruvian prospective cohort study.

Introduction: Dietary patterns (DPs) are associated with overall nutritional status and may alter the clinical prognosis of tuberculosis. This interaction can be further intricated by dysglycemia (i.e., diabetes or prediabetes). Here, we identified DPs that are more common with tuberculosis-dysglycemia and depicted their association with tuberculosis treatment outcomes. Methods: A prospective cohort study of persons with tuberculosis and their contacts was conducted in Peru. A food frequency questionnaire and a multidimensional systems biology-based analytical approach were employed to identify DPs associated with these clinical groups. Potential independent associations between clinical features and DPs were analyzed. Results: Three major DPs were identified. TB-dysglycemia cases more often had a high intake of carbohydrates (DP1). Furthermore, DP1 was found to be associated with an increased risk of unfavorable TB outcomes independent of other factors, including dysglycemia. Conclusion: Our findings suggest that the evaluation of nutritional status through DPs in comorbidities such as dysglycemia is a fundamental action to predict TB treatment outcomes. The mechanisms underlying the association between high intake of carbohydrates, dysglycemia, and unfavorable tuberculosis treatment outcomes warrant further investigation.

Saberes populares e produção de saúde: repensando práticas no cuidado materno-infantil / Popular knowledge production and health: rethinking practices in maternal and child care

Neste artigo, buscou-se analisar os principais saberes populares empregados na saúde materno-infantil, por gestantes de uma unidade de atenção primária à saúde, de Petrolina-PE. Estudo de abordagem qualitativa, exploratório e descritivo, com 12 gestantes, entre 17 e 40 anos, cadastradas na Unidade do Programa de Agentes Comunitários de Saúde (PACS), bairro Mandacarú, zona urbana de Petrolina-PE, escolhida devido à inserção cultural e à situação socioeconômica do bairro, o que favorece a introdução de práticas populares. Utilizou-se roteiro semiestruturado, de acordo com a análise temática de conteúdo. As gestantes relataram as principais crendices populares para o cuidado com a saúde materno-infantil, ensinadas, muitas vezes, por familiares mais velhos. Em muitas situações, não tendo acesso imediato às instituições de saúde, as mulheres optam pelos cuidados populares. O cuidado popular não deve ser a única fonte de informação, mas precisa estar aliado ao conhecimento científico ofertado pelos profissionais de saúde, não permitindo que a comunidade se exponha a riscos desnecessários e podendo cuidar da saúde do binômio de forma mais segura.

We sought to analyze the main popular knowledge workers in maternal and child health for pregnant women in a unit of primary health care, of Petrolina. Study of qualitative, exploratory and descriptive approach, with 12 pregnant women between 17 and 40 years, enrolled in the Program Unit of Community Health (PACS), Mandacarú district, urban area of Petrolina-PE, chosen due to cultural integration and the socioeconomic status of the neighborhood, which favors the introduction of popular practices. We used semi-structured, analyzed according to thematic content analysis. The women reported major popular beliefs to care for maternal and child health, taught, often by older family members. In many situations, not having immediate access health facilities, women opt for popular attention. The popular care should not be the only source of information, but it must be coupled with scientific knowledge, offered by health professionals, not allowing the community to expose yourself to unnecessary risks and can take care of the health of the binomial more safely.

A representação social e os significadosdos docentes sobre a síndrome de Burnout na dimensão da exaustão emocional / The representation and social meanings of teachers with burnout syndrome through the dimension of emotional exhaustion

A Síndrome de Burnout (SB) é um processo de cronificaçãoemocional do estresse laboral. A Representação Social (RS) é a formacomo a sociedade expressa a sua realidade. Buscou-se conhecer operfil sociodemográfico e a representação social dos docentes comSB, na dimensão da Exaustão Emocional (EE). Tratou-se de estudoexploratório e qualitativo com 06 docentes com diagnóstico de SB nadimensão da EE. Utilizou-se o questionário de Maslach (MBI–Ed)e entrevista semiestruturada com questões norteadoras, no períodode outubro a dezembro de 2010 com aprovação 276/2009 do Comitêde Ética da UNIFOR. Constam os resultados: 05 docentes dosexo masculino e 01 sexo feminino; sendo 03 casados, 02 solteirose 01 divorciado; a idade média de 37,8 anos; o tempo de docência9,1 anos e a escolaridade foi mestre (04 docentes). A análise dossignificados identificou 04 categorias: Relacionamento, expressa asrelações interpessoais; Tempo, relata a dificuldade de administração;Atividade Profissional, expressa o ato de ser professor; e Estresse,expressa os efeitos da docência. Observou-se uma relação diretacom os professores e o reconhecimento de uma realidade desconhecida,sujeitando-os a dificuldades no diagnóstico e tratamentoda síndrome, requerendo ações e medidas de prevenção e educaçãojunto aos docentes e a IES.

The Burnout Syndrome (SB) is the process of becoming chronicemotional stressed in work settings. The Social Representation(RS) is the way in which society expresses its reality. We soughtto understand the socio-demographic and social representation ofteachers with SB, through the dimension of Emotional Exhaustion(EE). It was an exploratory and qualitative research with 06teachers diagnosed with SB inside the scope of EE. We used thequestionnaire Maslach (MBI-Ed) and semi-structured interviewswith leading questions, from October to December 2010 withapproval 276/2009 of the Ethics Committee at UNIFOR. Theresults consist of: 05 male teachers and 01 female, being married03, 02 single and 01 divorced, the average age 37.8 years-old; timeteaching and schooling was about 9.1 years, Masters degree (04teachers). The analysis identified 04 categories for the results: Relationshipexpresses interpersonal relationships; Time, describes thedifficulties of administration; Professional Activity expresses the actof being a teacher, and stress, the effects of explicit teaching. Therewas a direct relationship with the teachers and the recognition ofan unknown reality, subjecting them to adversities for the diagnosisand treatment of the syndrome, requiring actions and measures forprevention and education among teachers and IES.