Growth after pediatric kidney transplantation: a 25-year study in a pediatric kidney transplant center.

OBJECTIVES: Growth failure is one of the major complications of pediatric chronic kidney disease. Even after a kidney transplant (KT), up to 50 % of patients fail to achieve the expected final height. This study aimed to assess longitudinal growth after KT and identify factors influencing it. METHODS: A retrospective observational study was performed. We reviewed the clinical records of all patients who underwent KT for 25 years in a single center (n=149) and performed telephone interviews. Height-for-age and body mass index (BMI)-for-age were examined at KT, 3 months, 6 months, 1 year, and 5 years post-transplant and at the transition to adult care. We evaluated target height, disease duration before KT, need and type of dialysis, recombinant human growth hormone pretransplant use, nutritional support, glomerular filtration rate (GFR), and cumulative corticosteroid dose. RESULTS: At transplant, the average height z-score was -1.38, and height z-scores showed catch-up growth at 6 months (z-score -1.26, p=0.006), 1 year (z-score -1.15, p<0.001), 5 years after KT (z-score -1.08, p<0.001), and on transition to adult care (z-score -1.22, p=0.012). Regarding BMI z-scores, a significant increase was also detected at all time points (p<0.001). After KT, GFR was significantly associated with height z-score (p=0.006) and BMI z-score (p=0.006). The height in transition to adult care was -1.28 SD compared to the target height. CONCLUSIONS: Despite the encouraging results regarding catch-up growth after KT in this cohort, results remain far from optimum, with a lower-than-expected height at the time of transition.

An allosteric redox switch involved in oxygen protection in a CO2 reductase.

Metal-dependent formate dehydrogenases reduce CO2 with high efficiency and selectivity, but are usually very oxygen sensitive. An exception is Desulfovibrio vulgaris W/Sec-FdhAB, which can be handled aerobically, but the basis for this oxygen tolerance was unknown. Here we show that FdhAB activity is controlled by a redox switch based on an allosteric disulfide bond. When this bond is closed, the enzyme is in an oxygen-tolerant resting state presenting almost no catalytic activity and very low formate affinity. Opening this bond triggers large conformational changes that propagate to the active site, resulting in high activity and high formate affinity, but also higher oxygen sensitivity. We present the structure of activated FdhAB and show that activity loss is associated with partial loss of the metal sulfido ligand. The redox switch mechanism is reversible in vivo and prevents enzyme reduction by physiological formate levels, conferring a fitness advantage during O2 exposure.

Impact of the Cationic Moiety of Ionic Liquids on Chemoselective Artificial Olfaction.

Ionogels and derived materials are assemblies of polymers and ionic liquids characterized by high stability and ionic conductivity, making them interesting choices as gas sensors. In this work, we assessed the effect of the ionic liquid moiety to generate ionogels and hybrid gels as electrical and optical gas sensors. Six ionic liquids consisting of a constant anion (chloride) and distinct cationic head groups were used to generate ionogels and hybrid gels and further tested as gas sensors in customized electronic nose devices. In general, ionogel-based sensors yielded higher classification accuracies of standard volatile organic compounds when compared to hybrid material-based sensors. In addition, the high chemical diversity of ionic liquids is further translated to a high functional diversity in analyte molecular recognition and sensing.

Effect of Polymer Hydrophobicity in the Performance of Hybrid Gel Gas Sensors for E-Noses.

Relative humidity (RH) is a common interferent in chemical gas sensors, influencing their baselines and sensitivity, which can limit the performance of e-nose systems. Tuning the composition of the sensing materials is a possible strategy to control the impact of RH in gas sensors. Hybrid gel materials used as gas sensors contain self-assembled droplets of ionic liquid and liquid crystal molecules encapsulated in a polymeric matrix. In this work, we assessed the effect of the matrix hydrophobic properties in the performance of hybrid gel materials for VOC sensing in humid conditions (50% RH). We used two different polymers, the hydrophobic PDMS and the hydrophilic bovine gelatin, as polymeric matrices in hybrid gel materials containing imidazolium-based ionic liquids, [BMIM][Cl] and [BMIM][DCA], and the thermotropic liquid crystal 5CB. Better accuracy of VOC prediction is obtained for the hybrid gels composed of a PDMS matrix combined with the [BMIM][Cl] ionic liquid, and the use of this hydrophobic matrix reduces the effect of humidity on the sensing performance when compared to the gelatin counterpart. VOCs interact with all the moieties of the hybrid gel multicomponent system; thus, VOC correct classification depends not only on the polymeric matrix used, but also on the IL selected, which seems to be key to achieve VOCs discrimination at 50% RH. Thus, hybrid gels' tunable formulation offers the potential for designing complementary sensors for e-nose systems operable under different RH conditions.

Carboxysome-Inspired Electrocatalysis using Enzymes for the Reduction of CO2 at Low Concentrations.

The electrolysis of dilute CO2 streams suffers from low concentrations of dissolved substrate and its rapid depletion at the electrolyte-electrocatalyst interface. These limitations require first energy-intensive CO2 capture and concentration, before electrolyzers can achieve acceptable performances. For direct electrocatalytic CO2 reduction from low-concentration sources, we introduce a strategy that mimics the carboxysome in cyanobacteria by utilizing microcompartments with nanoconfined enzymes in a porous electrode. A carbonic anhydrase accelerates CO2 hydration kinetics and minimizes substrate depletion by making all dissolved carbon available for utilization, while a highly efficient formate dehydrogenase reduces CO2 cleanly to formate; down to even atmospheric concentrations of CO2 . This bio-inspired concept demonstrates that the carboxysome provides a viable blueprint for the reduction of low-concentration CO2 streams to chemicals by using all forms of dissolved carbon.

The Biology of Lysosomes: From Order to Disorder.

Since its discovery in 1955, the understanding of the lysosome has continuously increased. Once considered a mere waste removal system, the lysosome is now recognised as a highly crucial cellular component for signalling and energy metabolism. This notable evolution raises the need for a summarized review of the lysosome's biology. As such, throughout this article, we will be compiling the current knowledge regarding the lysosome's biogenesis and functions. The comprehension of this organelle's inner mechanisms is crucial to perceive how its impairment can give rise to lysosomal disease (LD). In this review, we highlight some examples of LD fine-tuned mechanisms that are already established, as well as others, which are still under investigation. Even though the understanding of the lysosome and its pathologies has expanded through the years, some of its intrinsic molecular aspects remain unknown. In order to illustrate the complexity of the lysosomal diseases we provide a few examples that have challenged the established single gene-single genetic disorder model. As such, we believe there is a strong need for further investigation of the exact abnormalities in the pathological pathways in lysosomal disease.

Promoção do conforto da pessoa com cancro de cabeça e pescoço em fim de vida e família: intervenção de enfermagem / Promoting comfort for people with head and neck cancer at the end of life and their families: nursing intervention

O presente relatório foi desenvolvido no âmbito da unidade curricular de estágio com relatório do 3º semestre do 12º Curso de Mestrado/Especialidade em Enfermagem Médico-Cirúrgica na vertente de Enfermagem Oncológica. Exercendo funções num Serviço de Otorrinolaringologia e, contatando diariamente com pessoas com CCP, verifico, após reflexão pessoal, que esta população sofre um enorme impacto no seu conforto, em particular, no fim de vida, sendo uma perceção igualmente partilhada pelos colegas do serviço. Além disso, a equipa de enfermagem refere sentir dificuldades na prestação de cuidados promotores do conforto, nomeadamente, no controlo de sintomas do foro físico, psicológico, social e espiritual a esta população e sua família. Deste modo, com a elaboração deste relatório, pretendo demonstrar o processo de desenvolvimento de competências de enfermeiro especialista na intervenção de enfermagem à pessoa com CCP em fim de vida e sua família, contribuir para a melhoria da qualidade dos cuidados prestados e promover o seuconforto. Sustentada na metodologia de projeto, realizei três estágios onde, nos dois primeiros, potenciou-se um processo de desenvolvimento de competências técnicas, relacionais e pessoais para o cuidar da pessoa em fim de vida. No último estágio, apliquei o que foi desenvolvido em termos de competências de enfermeiro especialista bem como capacitei a equipa de enfermagem através da realização de duas formações onde foram apresentadas as intervenções de enfermagem promotoras do conforto à pessoa com CCP em fim de vida e família, conteúdos acedidos através da revisão da literatura e observação da prática de cuidados. Foram ainda elaborados e apresentados um guia orientador de cuidados dirigido aos enfermeiros do Serviço de ORL que será uma ferramenta chave para a prática bem como um protocolo de articulação com a EIHSCP que permitirá estruturar a resposta às necessidades de cuidados paliativos da pessoa com CCP através da parceria entre as equipas de enfermagem dos Serviços ORL ­ internamento e da EIHSCP, sendo que ambos irãopotenciar uma resposta mais precoce e de qualidade pela equipa de enfermagem e contribuir para a promoção do conforto da pessoa em fim de vida e família.

This report was developed within the internship curricular unit with report of the 3rd semester of the 12th Course of Master/Specialty in Medical-Surgical Nursing in the Oncological Nursing field. Performing functions in an Otorhinolaryngologist Service and contacting daily with CCP patients, I verified after a personal reflection, that this population suffers an enormous impact in its comfort, particularly, in the end of life. This perception is equally shared by the co-workers. Furthermore, the nursing team refers to have difficulties in the provision of care that maximize comfort, namely the control of symptoms of the physical, psychological, social and spiritual forum to this population and its family. This way, with the elaboration of this report, I intend to demonstrate the development process of skills of a specialist nurse in the nursing intervention to the person with CCP in end of life and its family, contributing to the improvement of the quality of the provided care and promotion of their comfort. Supported by the project methodology, three internships were made where, in the first two, it was strengthened a development process of technical, relationship and personal skills to the care of a person in end of life. In the last internship, I applied what was developed in terms of skills of specialist nurse as well as I enabled the nursing team through two trainings where it was disclosed the nursing interventions promoters of comfort to the person with CCP in end of life and family, contents assessed through the literature review and observation of practical cares. It was also made and presented a guiding guide of cares addressed to the nurses of the ORL Service which will be a key tool for the practicing as well as an articulation protocol with the EIHSCP, which will allow to organize the answer to the needs of palliative care of the person with CCP through the partnership between the nursing teams of the ORL Services ­ internment and the EIHSCP, both of which will potentiate an earlier and with more quality action by the nursing team as well as promote the comfort of the person in end of life and its family.

Psychological group intervention to support parenting: Qualitative study about needs and preferences of mothers with breast cancer.

PURPOSE: Parental worries and parenting stress can increase when a mother receives a breast cancer diagnosis. This study presents the findings of needs and preferences of mothers with breast cancer to inform the development of a group intervention program for mothers with breast cancer and other alternatives of support. METHODS: Using qualitative data from eighteen Portuguese women with at least one minor child when they received a breast cancer diagnosis, and content analysis on three focus groups transcripts, we uncover the participants' parenting needs and their perceptions of the potential benefits and the formal aspects of a group intervention. RESULTS: Mothers revealed that they need support on several parenting-related issues (e.g., communicating with the children about the mother's diagnosis, dealing with children's responses and difficult questions). They provided information about the potential benefits of group intervention and preferences regarding intervention content, sessions' structure, frequency, location, and timing. Some participants also suggested other types of support, such as online information and individual psychological support. CONCLUSIONS: The development of an intervention informed by the patients' needs and preferences can contribute to increasing its feasibility and efficacy. The findings indicated the specific parenting needs of Portuguese mothers with breast cancer, and it offered health professionals some important clues on how to support other family members.

Transição para a parentalidade: O impacto do nascimento do primeiro filho na vivência da conjugalidade do casal / Transition to parenthood: The impact of the birth of the first child on the couple's conjugal experience

Enquadramento: ao longo do seu ciclo vital, a família, vivencia transições e crises que exigem adaptações e transformações e o nascimento do primeiro filho integra uma dessas transições. Segundo Meleis, a transição revela uma mudança no estado de saúde, nas relações de papéis, nas expectativas ou habilidades. Os casais que decidem serem pais, para além de todas as adaptações que necessitam de realizar no espaço físico e de aceitação do novo membro, passam também por um processo de transição, a transição para a parentalidade. A transição do subsistema conjugal para o parental assume um papel preponderante, na qual os elementos são desafiados a assumirem novos papéis: mãe e pai. Objetivo: conhecer o impacto do nascimento do primeiro filho na vivência da conjugalidade do casal. Metodologia: estudo qualitativo exploratório-descritivo, de nível I. A amostra é não probabilística, tipo bola de neve, constituída por casais que aceitassem voluntariamente participar no estudo e cumprissem os critérios de inclusão definidos. A recolha de dados realizou-se através de uma entrevista semiestruturada ao casal, separadamente, para obtenção de respostas individualizadas. Os dados obtidos destas entrevistas foram depois analisados e categorizados segundo a análise de conteúdo de Bardin (Bardin, 2015). Resultados: da análise dos discursos dos participantes emergiram quatro categorias principais: Quotidiano de vida do casal; Vivência da conjugalidade; Vivência da sexualidade e Sentimento de preparação para a parentalidade. A transição para a parentalidade leva a reestruturação da dinâmica familiar e redefinição de papéis e, consequentemente, tem impacto na vivência da conjugalidade do casal. Assim, é possível realçar a importância e a necessidade de intervenção do enfermeiro especialista em ESMO no período pré e pós-parto, como mediador e promotor da vivência da parentalidade e da conjugalidade de forma equilibrada, sem distúrbios para a saúde de pais e criança.

Spectroscopic and Structural Characterization of Reduced Desulfovibrio vulgaris Hildenborough W-FdhAB Reveals Stable Metal Coordination during Catalysis.

Metal-dependent formate dehydrogenases are important enzymes due to their activity of CO2 reduction to formate. The tungsten-containing FdhAB formate dehydrogenase from Desulfovibrio vulgaris Hildenborough is a good example displaying high activity, simple composition, and a notable structural and catalytic robustness. Here, we report the first spectroscopic redox characterization of FdhAB metal centers by EPR. Titration with dithionite or formate leads to reduction of three [4Fe-4S]1+ clusters, and full reduction requires Ti(III)-citrate. The redox potentials of the four [4Fe-4S]1+ centers range between -250 and -530 mV. Two distinct WV signals were detected, WDV and WFV, which differ in only the g2-value. This difference can be explained by small variations in the twist angle of the two pyranopterins, as determined through DFT calculations of model compounds. The redox potential of WVI/V was determined to be -370 mV when reduced by dithionite and -340 mV when reduced by formate. The crystal structure of dithionite-reduced FdhAB was determined at high resolution (1.5 Å), revealing the same structural alterations as reported for the formate-reduced structure. These results corroborate a stable six-ligand W coordination in the catalytic intermediate WV state of FdhAB.

Elucidating Film Loss and the Role of Hydrogen Bonding of Adsorbed Redox Enzymes by Electrochemical Quartz Crystal Microbalance Analysis.

The immobilization of redox enzymes on electrodes enables the efficient and selective electrocatalysis of useful reactions such as the reversible interconversion of dihydrogen (H2) to protons (H+) and formate to carbon dioxide (CO2) with hydrogenase (H2ase) and formate dehydrogenase (FDH), respectively. However, their immobilization on electrodes to produce electroactive protein films for direct electron transfer (DET) at the protein-electrode interface is not well understood, and the reasons for their activity loss remain vague, limiting their performance often to hour timescales. Here, we report the immobilization of [NiFeSe]-H2ase and [W]-FDH from Desulfovibrio vulgaris Hildenborough on a range of charged and neutral self-assembled monolayer (SAM)-modified gold electrodes with varying hydrogen bond (H-bond) donor capabilities. The key factors dominating the activity and stability of the immobilized enzymes are determined using protein film voltammetry (PFV), chronoamperometry (CA), and electrochemical quartz crystal microbalance (E-QCM) analysis. Electrostatic and H-bonding interactions are resolved, with electrostatic interactions responsible for enzyme orientation while enzyme desorption is strongly limited when H-bonding is present at the enzyme-electrode interface. Conversely, enzyme stability is drastically reduced in the absence of H-bonding, and desorptive enzyme loss is confirmed as the main reason for activity decay by E-QCM during CA. This study provides insights into the possible reasons for the reduced activity of immobilized redox enzymes and the role of film loss, particularly H-bonding, in stabilizing bioelectrode performance, promoting avenues for future improvements in bioelectrocatalysis.

Fast CO2 hydration kinetics impair heterogeneous but improve enzymatic CO2 reduction catalysis.

The performance of heterogeneous catalysts for electrocatalytic CO2 reduction suffers from unwanted side reactions and kinetic inefficiencies at the required large overpotential. However, immobilized CO2 reduction enzymes-such as formate dehydrogenase-can operate with high turnover and selectivity at a minimal overpotential and are therefore 'ideal' model catalysts. Here, through the co-immobilization of carbonic anhydrase, we study the effect of CO2 hydration on the local environment and performance of a range of disparate CO2 reduction systems from enzymatic (formate dehydrogenase) to heterogeneous systems. We show that the co-immobilization of carbonic anhydrase increases the kinetics of CO2 hydration at the electrode. This benefits enzymatic CO2 reduction-despite the decrease in CO2 concentration-due to a reduction in local pH change, whereas it is detrimental to heterogeneous catalysis (on Au) because the system is unable to suppress the H2 evolution side reaction. Understanding the role of CO2 hydration kinetics within the local environment on the performance of electrocatalyst systems provides important insights for the development of next-generation synthetic CO2 reduction catalysts.

Understanding the local chemical environment of bioelectrocatalysis.

Bioelectrochemistry employs an array of high-surface-area meso- and macroporous electrode architectures to increase protein loading and the electrochemical current response. While the local chemical environment has been studied in small-molecule and heterogenous electrocatalysis, conditions in enzyme electrochemistry are still commonly established based on bulk solution assays, without appropriate consideration of the nonequilibrium conditions of the confined electrode space. Here, we apply electrochemical and computational techniques to explore the local environment of fuel-producing oxidoreductases within porous electrode architectures. This improved understanding of the local environment enabled simple manipulation of the electrolyte solution by adjusting the bulk pH and buffer pKa to achieve an optimum local pH for maximal activity of the immobilized enzyme. When applied to macroporous inverse opal electrodes, the benefits of higher loading and increased mass transport were employed, and, consequently, the electrolyte adjusted to reach -8.0 mA ⋅ cm-2 for the H2 evolution reaction and -3.6 mA ⋅ cm-2 for the CO2 reduction reaction (CO2RR), demonstrating an 18-fold improvement on previously reported enzymatic CO2RR systems. This research emphasizes the critical importance of understanding the confined enzymatic chemical environment, thus expanding the known capabilities of enzyme bioelectrocatalysis. These considerations and insights can be directly applied to both bio(photo)electrochemical fuel and chemical synthesis, as well as enzymatic fuel cells, to significantly improve the fundamental understanding of the enzyme-electrode interface as well as device performance.

Tracking W-Formate Dehydrogenase Structural Changes During Catalysis and Enzyme Reoxidation.

Metal-dependent formate dehydrogenases (Fdh) catalyze the reversible conversion of CO2 to formate, with unrivalled efficiency and selectivity. However, the key catalytic aspects of these enzymes remain unknown, preventing us from fully benefiting from their capabilities in terms of biotechnological applications. Here, we report a time-resolved characterization by X-ray crystallography of the Desulfovibrio vulgaris Hildenborough SeCys/W-Fdh during formate oxidation. The results allowed us to model five different intermediate structures and to chronologically map the changes occurring during enzyme reduction. Formate molecules were assigned for the first time to populate the catalytic pocket of a Fdh. Finally, the redox reversibility of DvFdhAB in crystals was confirmed by reduction and reoxidation structural studies.

A Semi-artificial Photoelectrochemical Tandem Leaf with a CO2 -to-Formate Efficiency Approaching 1 .

Semi-artificial photoelectrochemistry can combine state-of-the-art photovoltaic light-absorbers with enzymes evolved for selective fuel-forming reactions such as CO2 reduction, but the overall performance of such hybrid systems has been limited to date. Here, the electrolyte constituents were first tuned to establish an optimal local environment for a W-formate dehydrogenase to perform electrocatalysis. The CO2 reductase was then interfaced with a triple cation lead mixed-halide perovskite through a hierarchically structured porous TiO2 scaffold to produce an integrated photocathode achieving a photocurrent density of -5 mA cm-2 at 0.4 V vs. the reversible hydrogen electrode during simulated solar light irradiation. Finally, the combination with a water-oxidizing BiVO4 photoanode produced a bias-free integrated biophotoelectrochemical tandem device (semi-artificial leaf) with a solar CO2 -to-formate energy conversion efficiency of 0.8 %.

Heavy Metals Removal from Aqueous Solutions by Multiwall Carbon Nanotubes: Effect of MWCNTs Dispersion.

Carbon nanotubes (CNTs) are one of the most studied nanoparticles due to their physical, chemical and electronic properties. However, strong Van der Waals bonds, which promote CNTs aggregation are usually present, affecting their unique properties. Avoiding CNTs aggregation is one of the main difficulties when using these nanoparticles. Regarding the adsorption capacity of CNTs, the tendency of CNTs to aggregate decreases the surface area available to retain contaminants. One way to overcome this issue is by changing the surface energy of CNTs through chemical (covalent and noncovalent methods) or mechanical stabilization, but there is not yet a unique solution to solve this problem. In this work, a chemical noncovalent method (addition of surfactants) combined with mechanical energy (ultrasounds) was applied for CNTs stabilization, and the influence in heavy metal ions removal, Pb (II), Cu (II), Ni (II) and Zn (II), an area of high environmental relevance, was evaluated. It was proved that high amounts of metals could be removed from water during the first eighteen hours. Competitive adsorption between heavy metals, during adsorption tests with the simultaneous presence of all ions, was also studied and it was possible to prove that the electronegativity and atomic radius of cations influence their removal. Pb (II) and Cu (II) were the metals removed in higher percentages, and Ni (II) and Zn (II) were the metals less removed during competitive adsorption. Finally, the results obtained show that MWCNTs, if adequately dispersed, present a good solution for the treatment of water contaminated with highly toxic heavy metals, even when using very low concentrations of Multiwall Carbon Nanotubes (MWCNTs).

Generation and characterization of induced pluripotent stem cells heterozygous for the Portuguese BRCA2 founder mutation.

Women who inherit heterozygous mutations in the BRCA2 gene have an increased risk of developing cancer, mainly breast and ovarian tumors. A particular BRCA2 mutation (c.156_157insAlu) is exclusively found in families of Portuguese ancestry and is present in approximately 30% of all Portuguese families with hereditary breast and ovarian cancers. We report the generation and characterization of the first iPSC line from a female donor harboring the Portuguese BRCA2 founder mutation. Skin fibroblasts were reprogrammed using a non-integrative Sendai virus. These iPSCs are a valuable tool to study the origin of BRCA2-associated cancer in its earliest phases.

Generation and characterization of induced pluripotent stem cells from a family carrying the BRCA1 mutation c.3612delA.

How BRCA1 germline mutations predispose to cancer remains poorly understood. Induced pluripotent stem cells (iPSCs) represent an emerging model to investigate the molecular mechanisms underlying malignant transformation in primary cells from individuals who are carriers of deleterious mutations in the BRCA1 gene. Here we report the generation and characterization of iPSC lines from a female donor harboring a germline c.3612delA mutation in the BRCA1 gene and her daughter who does not carry the mutation. Skin fibroblasts were reprogrammed using non-integrative Sendai virus and characterized for their pluripotent properties. These iPSCs are a valuable cellular model for personalized pre-clinical research in the context of BRCA1 mutant hereditary cancers.

Formate Dehydrogenases Reduce CO2 Rather than HCO3- : An Electrochemical Demonstration.

Mo/W formate dehydrogenases catalyze the reversible reduction of CO2 species to formate. It is thought that the substrate is CO2 and not a hydrated species like HCO3- , but there is still no indisputable evidence for this, in spite of the extreme importance of the nature of the substrate for mechanistic studies. We devised a simple electrochemical method to definitively demonstrate that the substrate of formate dehydrogenases is indeed CO2 .