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Karst ecosystems offer a wealth of ecosystem services, but their protection is increasingly challenging due to degradation and land-use conversion, including limestone mining. This study investigates the water provision service derived from karst ecosystems threatened by limestone mining in the Watuputih groundwater basin, Central Java, Indonesia. Water supply was quantified by measuring water discharge rates from major springs around the basin. Water usage was quantified for household consumption, agriculture, and recreation. This study also measured water infiltration rates in mining and non-mining areas to indicate the effects of limestone mining to hydrological processes. This study identified three primary springs around the basin: Sumber Seribu spring, Brubulan spring, and Kalutan spring, with discharge rates of 1080 L per second, 85 L per second, and 0.76 L per second, respectively. A local water company extracts water from Sumber Seribu spring at a rate of 80 L per second to supply approximately 57,600 individuals. The water supply from the three springs can irrigate approximately 1594 ha of rice fields. Water from Sumber Seribu spring also supports recreational activities in Sumber Semen recreation park, attracting an average of 19,173 visitors per year. This study revealed a complete impairment of soil's water infiltration capacity in limestone mining areas. These findings underscore the pressing need to safeguard the Watuputih groundwater basin and to mitigate the detrimental effects of limestone mining on hydrological processes. This involves designating the Watuputih karst ecosystem as a protected area, implementing Payment for Ecosystem Services (PES) programs, and restoring degraded post-mining sites.

Objective: This study applied the Family Systems Illness Model to examine how child disorder severity influences mental health in mothers and fathers of children with chronic (mainly developmental) disorders (CD). Methods: We measured parental mental health and perceived child disorder severity among 204 mothers and 125 fathers of 220 children with CD and compared the mental health scores with norms. We analyzed how much of the variance in parental mental health was explained by child disorder severity, including discrepancy between maternally and paternally perceived severity. Results: Compared to norms, we found elevated mental health problems in both mothers (d = 0.45) and fathers (d = 0.20) of children with CD. Mothers had higher scores than fathers on both mental health problems (d = 0.63) and severity (d = 0.43). Perceived disorder severity was similarly associated with mental health problems for mothers (β = 0.23) and fathers (β = 0.34). Discrepancy between maternal and paternal perceived disorder severity did not influence parental mental health. Conclusion: Findings suggest gender-specific challenges in parenting children with CD. Subjective perception of disorder severity plays a substantial role for parental mental health. Innovation: This comparative study of mothers and fathers contributes to a predominantly mother-focused field.

Objective: The purpose of this study was to investigate how parents of children with complex care needs conceptualize burnout from the perspective of parents themselves. Methods: We conducted semi-structured interviews with 38 parents, selected for maximal variation in parental, child, and family characteristics. Inductive thematic analysis was employed. Results: Burnout was conceptualized as encompassing three themes: having a reoccurring long-term nature, commencing with symptoms of stress progressing into exhaustion, and ending in a survival mode wherein parents worked hard to project an image of everything being well and under control (fighting) while distancing physically and emotionally from others and themselves (fleeing). Conclusion: Burnout involves specific aspects of caregiving and parenting, such as long-term responsibility for the child, which cannot be relinquished. Furthermore, burnout may also be ‘hidden’: not always showing to the outside world, which requires extra attention and vigilance among parent's informal and formal networks. Awareness of the various interpretations of the term may foster constructive communication. Innovation: Focusing on parents’ individual experiences has illuminated new aspects of burnout. By purposively sampling a variety of parents of children with complex care needs, a broader understanding of the meaning of the term ‘burnout’ from the perspective of parents was achieved.

Objective: Serious games can serve as easily accessible interventions to support siblings of children with disabilities, who are at risk of developing mental health problems. The Dutch serious game ‘Broodles’ was developed for siblings aged 6–9 years. The current study aims to assess the cultural applicability, desirability, feasibility, and acceptability of ‘Broodles’ in Norway. Methods: Norwegian siblings (N = 16) aged 6–13 years and parents (N = 12) of children with intellectual disabilities assessed the game. Their feedback data from interviews and questionnaires were sorted using a model of engagement factors in serious games. Results: At pre-use, participants showed interest in the game, and after initial use the participants were overall positive about the format, content and objectives, including validation of emotions and recognition. The participants had suggestions for improved engagement and feasibility. Conclusion: The game was found to be culturally applicable, desirable and acceptable, although Norwegian translation is necessary for further evaluation. Recommendations to enhance engagement were provided, including suggestions to play the game with parents or in a group. Innovation: This initial assessment of the serious game Broodles in a non-Dutch setting shows promise for an innovative way of supporting siblings of children with disabilities.

Abstract Nature's contributions to people (NCP) are essential for the production and trade of agricultural, forestry and fishery commodities. Often, there is a spatial disconnect between consumers and the natural systems where the commodities are produced. Traded agricultural products are therefore dependent on nature and NCP in their region of origin. The dependencies of agricultural products on NCP are, however, insufficiently recognised by consumers and are rarely considered in global environmental governance and trade policies along value chains. Here, we synthesise studies highlighting dependencies of agricultural products on NCP in their origin locations to identify opportunities and challenges in quantifying their contribution in sustaining trade flows. We suggest three methodological steps for quantifying NCP dependencies in international agricultural trade: spatial mapping of NCP supply and demand, linking NCP to agricultural trade flows, and tracing trade flows. Each methodological step requires further development and harmonisation to enable a complete accounting of how international agricultural trade depends on NCP. Given the lack of knowledge and data on how NCP support agricultural trade, social and environmental trade‐offs of natural resource management are currently hard to quantify. Quantifying the role of NCP dependencies of traded agricultural products can support their sustainable management, contribute to supply chain accountability and serve as input to sustainable natural resource governance and foster responsibility and equity in supply chains. Read the free Plain Language Summary for this article on the Journal blog.

RESUMO A lignificação é um processo bioquímico que abrange desde a formação dos monolignóis até a polimerização da lignina na parede celular. Além do apoio ao sistema estrutural da parede celular, defesa física e química, a lignina participa no processo de transporte de água no floema vascular e nas células do xilema. As estruturas moleculares das ligninas mostram-se variações complexas de acordo com sua composição. A biossíntese da lignina é composta de duas etapas. A primeira, consta da participação de uma série de enzimas como: PAL, C4H, 4CL, C3H, OMT, F5H, CCR e CAD, que catalisam a formação dos precursores intermediários e finais dentro do compartimento citoplasmático. Durante a formação desses precursores algumas dessas enzimas atuam sobre o núcleo aromático, introduzindo hidroxilas em C-3 e C-5 e as metilando em seguida, enquanto outras promovem a redução da cadeia lateral. Estudos demonstram que a regulação destas enzimas podem modificar a arquitetura molecular e o grau de polimerização da lignina. Atualmente técnicas apuradas de transgenia são usadas para regular as atividades enzimáticas durante a formação da lignina, resultando em diversos benefícios para o setor florestal, agropecuária e meio ambiente.

RESUMO A madeira é um produto originado de um metabolismo bioquímico complexo de uma árvore. Esse metabolismo tem sido parcialmente descrito com base em estudos químicos, bioquímicos, enzimáticos e genômicos. A lignificação, por exemplo, é um processo final de uma via metabólica expressamente associada à formação do lenho, ativando os mecanismos do desenvolvimento geral e principalmente da diferenciação de determinados tecidos. Esse processo de formação xilemática recai sobre um controle de fatores altamente diversificados como nutrição, doenças e sistema hormonal. Esta revisão apresenta os fitohormônios como agentes reguladores do processo de formação da madeira. Estes fitohormônios são substâncias especiais que controlam vários processos fisiológicos e morfológicos de uma planta, assumindo grande importância sobre o contexto anatômico, bioquímico, fisiológico e genético. Em alguns, casos o efeito sinergístico sobre a xilogênese controla o processo de lignificação, por exemplo, na regulação da atividade da peroxidase na parede celular.

Resumo O objetivo da pesquisa foi propor um modelo sistemático de identificação de madeiras através de análise metabolômica por Ressonância Magnética Nuclear do 13C (RMN 13C) constituindo um banco de dados de 13C. Neste trabalho foram utilizados os extratos obtidos com ciclohexano de madeiras do híbrido E. urograndis. Quatro espécimes com aproximadamente 15 anos de idades foram coletados em diferentes localidades. Os dados de RMN 13C mostraram que os espectros dos extratos ciclohexano da madeira do cerne (DAP) foram os mais representativos para o estudo do E. urograndis devido ao número de absorções verificadas. Com os dados foi possível traçar o perfil espectral comum para o híbrido do E. urograndis de cada região anatômica (alburno, zona de transição e cerne).

RESUMO Aevolução do tecido vascular de plantas data de 450 milhões anos atrás. Durante a evolução aconteceram várias ocorrências de natureza botânica. Uma das ocorrências na diferenciação nas plantas vasculares é, por exemplo, a lignificação, processo que caracteriza a fase final da diferenciação celular. Para o entendimento do desenvolvimento vascular, são usadas abordagens de cunho fisiológico, bioquímico e molecular. Estas abordagens têm sido possíveis em decorrência do uso de plantas que apresentam boa visualização, adaptabilidade em condições de laboratório e crescimento rápido como é o caso do Arabidopsis, Coleus, Zinnia e Populus, que são modelos padrões para o estudo de diferenciação vascular. Com a disponibilidade de tecnologia molecular será possível avançar no conhecimento dos mecanismos de controle que dirigem e definem o tipo de organização do tecido vascular, assim como expressões de genes participativos da fase de diferenciação.

ABSTRACT This communication turn on the use of Solanun gilo (Solanaceae) for lignification test on the nutritional point of view. This plant was chosen due its fast growth, high calcium mobility and low lignin content (15,51%). The experiment was carried out using calcium sulfate (CaSO4) and calcium chloride (CaCl2) for weekly and biweekly application. The treated plants with CaSO4/CaCl2 (biweekly application) showed 4% of additional lignin content. High syringyl unit concentration was also verified at Guaiacyl: Syringyl ratio (G: S) of 0.8:1 and 1.2:1, for weekly and biweekly application, respectively. The estimation of the lignin content and its composition were performed by Klason and infrared spectroscopy methods.

Abstract Background Continuous positive airway pressure (CPAP) is the mainstay of treatment for obstructive sleep apnea (OSA). However, data about its effect on the upper airway, especially the epiglottis, are scarce. The aim of this study was to investigate the changes in upper airway dimensions and inspiratory flow in response to incremental pressure levels. Methods This is a secondary analysis of a prospective clinical trial in which patients with moderate to severe OSA underwent drug-induced sleep endoscopy with simultaneous recordings of flow and mask pressure. CPAP was titrated in small increments. For each pressure level a representative 3-breath segment was selected to determine specific flow features. The corresponding endoscopic footage was reviewed to assess the degree of upper airway collapse in a semi-quantitative manner. Results A total of 214 breath segments were obtained from 13 participants (median [Q1–Q3]; apnea-hypopnea index, 24.9 [20.1–43.9] events/h; body mass index 28.1 [25.1–31.7] kg/m²). CPAP significantly increased cross-sectional dimensions of the soft palate, lateral walls and tongue base, but not of the epiglottis, and induced epiglottis collapse in one subject. Increased pressure improved peak inspiratory flow and median ventilation in all patients, even in the presence of persistent epiglottis collapse. Conclusion CPAP does not effectively address epiglottis collapse in patients with OSA. However, it normalizes inspiratory flow regardless of its effect on the epiglottis. This clinical trial was registered on January 18th, 2020 on ClinicalTrials.gov with identifier NCT04232410.

Abstract Background Siblings of children with disabilities also need support. However, there are only a few evidence-based interventions for these siblings. The current study aims to assess the effectiveness of a newly developed serious game for young siblings of children with intellectual disability (ID) and/or visual impairment (VI). This serious game is hypothesized to improve sibling’s quality of life, adjustment to their brother’s or sister’s disability, and multiple aspects of psychosocial well-being. Methods The intervention consists of a serious game called “Broodles” (in Dutch: “Broedels”) that helps children to recognize and deal with thoughts, feelings, and difficult situations. The game consists of eight 20-minute levels that all have the same structure with eight game elements. Each level addresses a domain of sibling quality of life and combines animations, mini-documentaries, fun mini-games, and multiple-choice questions. In addition to the game, siblings make a worksheet after playing each level. In order to support the child, the parents or caregivers receive a short brochure with information and tips. The effectiveness of the intervention will be investigated among a sample of 154 children aged 6–9 years and their parents or caregivers, using a two-arm parallel RCT design. The experimental group will play the serious game “Broodles” over a period of 4 weeks, whereas the control group will be placed on a waiting list. Assessments will take place at three time points: pre-test (week 1), post-test (week 5), and follow-up (weeks 12–14). At each timepoint, children and parents will complete several questionnaires on quality of life and different aspects of psychosocial well-being. In addition, children will make drawings to assess the sibling relationship. Next to that, parents and children will answer closed and open-ended questions about the sibling adjustment to their brother or sister’s disability. Finally, parents and children will evaluate the serious game through closed and open-ended questions. Discussion This study contributes to the knowledge about sibling interventions and serious games. Additionally, if the serious game is proven to be effective, it will be a readily available, easily accessible, and free of charge intervention for siblings. Trial registration ClinicalTrials.gov, NCT05376007, registered prospectively on April 21, 2022.

Encouraged by randomized controlled trials demonstrating non-inferiority of transfemoral transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) across all surgical risk categories, there has been a dramatic increase in the use of TAVI in a younger patient cohort with severe aortic stenosis, endorsed by both European and American Cardiac Societies. However, the standard use of TAVI in younger, less co-morbid patients with a longer life expectancy can only be supported if there is sound data demonstrating long-term durability of transcatheter aortic valves (TAVs). In this article, we have reviewed available randomized and observational registry clinical data pertaining to TAV long-term durability, placing emphasis on trials and registries using the new standardized definitions of bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF). Despite inherent difficulties in interpreting the available data, the determination reached is that the risk of structural valve deterioration (SVD) is potentially lower after TAVI than SAVR at 5 to 10 years, and that the two treatment modalities have a similar risk of BVF. This supports the adoption of TAVI in younger patients evident in current practice. However, the routine use of TAVI in younger patients with bicuspid aortic valve stenosis should be cautioned due to insufficient long-term TAV durability data in this particular patient population. Finally, we highlight the importance of future research into the unique potential mechanisms that can potentially contribute to TAV degeneration.

Abstract Engineered living microtissues such as cellular spheroids and organoids have enormous potential for the study and regeneration of tissues and organs. Microtissues are typically engineered via self‐assembly of adherent cells into cellular spheroids, which are characterized by little to no cell–material interactions. Consequently, 3D microtissue models currently lack structural biomechanical and biochemical control over their internal microenvironment resulting in suboptimal functional performance such as limited stem cell differentiation potential. Here, this work report on stimuli‐responsive cell‐adhesive micromaterials (SCMs) that can self‐assemble with cells into 3D living composite microtissues through integrin binding, even under serum‐free conditions. It is demonstrated that SCMs homogeneously distribute within engineered microtissues and act as biomechanically and biochemically tunable designer materials that can alter the composite tissue microenvironment on demand. Specifically, cell behavior is controlled based on the size, stiffness, number ratio, and biofunctionalization of SCMs in a temporal manner via orthogonal secondary crosslinking strategies. Photo‐based mechanical tuning of SCMs reveals early onset stiffness‐controlled lineage commitment of differentiating stem cell spheroids. In contrast to conventional encapsulation of stem cell spheroids within bulk hydrogel, incorporating cell‐sized SCMs within stem cell spheroids uniquely provides biomechanical cues throughout the composite microtissues’ volume, which is demonstrated to be essential for osteogenic differentiation.

Summary: Wilms’ tumor protein 1 (WT1) is a tumor-associated antigen overexpressed in various cancers. As a self-antigen, negative selection reduces the number of WT1-specific T cell receptors (TCRs). Here, we provide a protocol to generate WT137-45-specific TCRs using healthy human peripheral blood mononuclear cells. We describe the expansion of WT1-specific T cell clones by two consecutive in vitro stimulations with autologous WT137-45-pulsed dendritic cells and peripheral blood lymphocytes. We then detail the detection with human leukocyte antigen/WT137-45 tetramers. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background People with mild to borderline intellectual disabilities (MBIDs) face challenges in social functioning, possibly as a result of limited mentalising abilities such as reflecting on the behaviour of themselves and others. Reflective functioning in people with MBIDs has not yet been investigated due to a lack of instruments. The Reflective Functioning Questionnaire (RFQ) is a seemingly easy adaptable, short self-report questionnaire. The aim of the present, explorative study was to adapt the RFQ for people with MBIDs and investigate the psychometric properties and correlations with other mentalising related constructs. The formulation of the items was adapted to the target group and items were added to broaden the scope towards reflection on both the self and other. Method Participants were 159 adults with MBIDs who completed a Dutch-translated and easy-to-read RFQ with five supplemental items, a questionnaire for autistic traits, a self-report questionnaire assessing perspective taking and two performance-based measures assessing emotion recognition and Theory of Mind. Results Confirmatory factor analysis confirmed the factor structure of the RFQ and revealed a two-factor structure with a Self and Other subscale. Generally satisfactory internal consistency and test-retest reliability were found. Explorative results showed correlations of the RFQ-8 and RFQ subscales with autistic traits and between the RFQ Other and perspective taking. Conclusions This explorative study is the first testing psychometric properties of the RFQ as a self-report questionnaire for assessing reflective functioning in adults with MBIDs. This step is relevant in gaining more scientific knowledge on assessing mentalising in people with MBIDs.

Background The association between perceived ethnic discrimination (PED) and mental health conditions is well studied. However, less is known about the association between PED and suicidal ideation, or the role of positive psychosocial factors in this association. Aims To examine the association between PED and suicidal ideation among ethnic minority groups in Amsterdam, The Netherlands, and investigate whether ethnicity and mastery (people's extent of feeling in control of their lives and environment) moderate this association. Method Cross-sectional data from the multi-ethnic HELIUS study were analysed (n = 17 053) for participants of South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin. PED was measured using the Everyday Discrimination Scale, suicidal ideation using item 9 of the Patient Health Questionnaire-9 and mastery using the Pearlin–Schooler Mastery Scale. Results Logistic regression analyses demonstrated a small positive association between PED and suicidal ideation (OR = 1.068, 95% CI 1.059–1.077), which did not differ among ethnic minority groups. Mastery did not moderate the association between PED and suicidal ideation among the ethnic minority groups. Conclusions Our findings support the hypothesis that PED is associated with suicidal ideation and this association does not significantly vary between ethnic minority groups. Although higher levels of mastery were associated with lower suicidal ideation, mastery did not moderate the relationship between PED and suicidal ideation. Besides targeting ethnic discrimination as a societal problem, future longitudinal research is needed to investigate whether interventions aimed at improving mastery could reduce suicidal ideation in ethnic minority groups.

Rheumatic diseases, such as osteoarthritis and rheumatoid arthritis, affect over 750 million people worldwide and contribute to approximately 40% of chronic pain cases. Inflammation and tissue damage contribute to pain in rheumatic diseases, but pain often persists even when inflammation/damage is resolved. Mechanisms that cause this persistent pain are still unclear. Mitochondria are essential for a myriad of cellular processes and regulate neuronal functions. Mitochondrial dysfunction has been implicated in multiple neurological disorders, but its role in sensory processing and pain in rheumatic diseases is relatively unexplored. This review provides a comprehensive understanding of how mitochondrial dysfunction connects inflammation and damage-associated pathways to neuronal sensitization and persistent pain. To provide an overall framework on how mitochondria control pain, we explored recent evidence in inflammatory and neuropathic pain conditions. Mitochondria have intrinsic quality control mechanisms to prevent functional deficits and cellular damage. We will discuss the link between neuronal activity, mitochondrial dysfunction and chronic pain. Lastly, pharmacological strategies aimed at reestablishing mitochondrial functions or boosting mitochondrial dynamics as therapeutic interventions for chronic pain are discussed. The evidence presented in this review shows that mitochondria dysfunction may play a role in rheumatic pain. The dysfunction is not restricted to neuronal cells in the peripheral and central nervous system, but also includes blood cells and cells at the joint level that may affect pain pathways indirectly. Pre-clinical and clinical data suggest that modulation of mitochondrial functions can be used to attenuate or eliminate pain, which could be beneficial for multiple rheumatic diseases.

BackgroundChild maltreatment is a common negative experience and has potential long-lasting adverse consequences for mental and physical health, including increased risk for major depressive disorder (MDD) and metabolic syndrome. In addition, child maltreatment may increase the risk for comorbid physical health conditions to psychiatric conditions, with inflammation as an important mediator linking child maltreatment to poor adult health. However, it remains unresolved whether experiencing child maltreatment increases the risk for the development of comorbid metabolic syndrome to MDD. Therefore, we investigated whether child maltreatment increased the risk for comorbid metabolic syndrome to depressed mood. Subsequently, we examined whether C-reactive protein (CRP), as an inflammatory marker, mediated this association. In addition, we investigated whether effects differed between men and women.MethodsAssociations were examined within cross-sectional data from the multiethnic HELIUS study (N = 21,617). Adult residents of Amsterdam, Netherlands, self-reported on child maltreatment (distinct and total number of types experienced before the age of 16 years) as well as current depressed mood (PHQ-9 score ≥ 10), and underwent physical examination to assess metabolic syndrome. The CRP levels were assessed in N = 5,998 participants. Logistic and linear regressions were applied for binary and continuous outcomes, respectively. All analyses were adjusted for relevant demographic, socioeconomic, and lifestyle characteristics, including ethnicity.ResultsA higher number of maltreatment types as well as distinct types of emotional neglect, emotional abuse, and sexual abuse were significantly associated with a higher risk for current depressed mood. Child maltreatment was not significantly associated with the risk for metabolic syndrome in the whole cohort, nor within individuals with depressed mood. As child maltreatment was not significantly associated with the CRP levels, subsequent mediation analyses were not performed. No significant moderating effects by sex were observed.ConclusionIn this multiethnic urban cohort, child maltreatment was associated with a higher risk for depressed mood. Contrary to our expectations, child maltreatment was not significantly associated with an increased risk for metabolic syndrome, neither in the whole cohort nor as a comorbid condition in individuals with depressed mood. As the data were cross-sectional and came from a non-clinical adult population, longitudinal perspectives in relation to various stages of the investigated conditions were needed with more comprehensive assessments of inflammatory markers.

Only very few enzymes are known to catalyze protein histidine methylation. Here, the authors show that METTL9 is responsible for most 1-methylhistidine modifications in mouse and human proteomes, and characterize METTL9′s substrate specificity and potential cellular functions.