RESUMEN
L-Arabinose (L-Ara) is a plant-specific sugar found in cell wall polysaccharides, proteoglycans, glycoproteins, and small glycoconjugates, which play physiologically important roles in cell proliferation and other essential cellular processes. L-Ara is synthesized as UDP-L-arabinose (UDP-L-Ara) from UDP-xylose (UDP-Xyl) by UDP-Xyl 4-epimerases (UXEs), a type of de novo synthesis of L-Ara unique to plants. In Arabidopsis, the Golgi-localized UXE AtMUR4 is the main contributor to UDP-L-Ara synthesis. However, cytosolic bifunctional UDP-glucose 4-epimerases (UGEs) with UXE activity, AtUGE1, and AtUGE3 also catalyze this reaction. For the present study, we first examined the physiological importance of bifunctional UGEs in Arabidopsis. The uge1 and uge3 mutants enhanced the dwarf phenotype of mur4 and further reduced the L-Ara content in cell walls, suggesting that bifunctional UGEs contribute to UDP-L-Ara synthesis. Through the introduction of point mutations exchanging corresponding amino acid residues between AtUGE1 with high UXE activity and AtUGE2 with low UXE activity, two mutations that increase relative UXE activity of AtUGE2 were identified. The crystal structures of AtUGE2 in complex forms with NAD+ and NAD+/UDP revealed that the UDP-binding domain of AtUGE2 has a more closed conformation and smaller sugar-binding site than bacterial and mammalian UGEs, suggesting that plant UGEs have the appropriate size and shape for binding UDP-Xyl and UDP-L-Ara to exhibit UXE activity. The presented results suggest that the capacity for cytosolic synthesis of UDP-L-Ara was acquired by the small sugar-binding site and several mutations of UGEs, enabling diversified utilization of L-Ara in seed plants.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Pared Celular , Citosol , UDPglucosa 4-Epimerasa , Azúcares de Uridina Difosfato , Arabidopsis/genética , Arabidopsis/enzimología , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Citosol/metabolismo , Citosol/enzimología , Azúcares de Uridina Difosfato/metabolismo , Pared Celular/metabolismo , UDPglucosa 4-Epimerasa/genética , UDPglucosa 4-Epimerasa/metabolismo , Mutación , Uridina Difosfato Xilosa/metabolismo , Uridina Difosfato Xilosa/genéticaRESUMEN
PURPOSE OF THE REVIEW: Children and adolescents with cancer, along with their parents and other informal caregivers, often report using complementary and alternative medicine (CAM) during active oncology and hemato-oncology treatment. Some adopt an "alternative" approach to conventional medical care, which often entails the use of these practices without the knowledge of the treating pediatrician. In contrast, many others search for consultation provided by a pediatric integrative oncology (IO) practitioner working with the conventional medical team. IO seeks to provide evidence-based complementary medicine therapies, many of which have been shown to augment conventional supportive and palliative care, while ensuring the patient's safety. The present narrative review examines the current state of and future direction for the IO setting of care. RECENT FINDINGS: A large body of published clinical research supports the effectiveness of leading Pediatric IO modalities, while addressing potential safety-related concerns. Despite the growing amount of clinical research supporting the beneficial effects and implementation of Pediatric IO models of care, there is still a need for further studies in order to establish clinical guidelines in the treatment of children and adolescents with cancer. Such IO-directed guidelines will need to address both the effectiveness and the safety of the CAM modalities being used in pediatric oncology and hemato-oncology settings, promoting a better understanding among pediatric healthcare professionals and helping them understand the indications for referral to the IO treatment service.
Asunto(s)
Terapias Complementarias , Medicina Integrativa , Neoplasias , Humanos , Neoplasias/terapia , Niño , Medicina Integrativa/métodos , Terapias Complementarias/métodos , Adolescente , Pediatría/métodos , Oncología Médica/métodosRESUMEN
BACKGROUND: There are evidence gaps in the management of pediatric cough, particularly for acute pediatric cough. This study had two aims: to identify therapeutic principles and unmet needs in the treatment of cough in pediatric patients (internationally), and to consider the evidence required to address these unmet needs. METHODS: A MEDLINE/PubMed database search was performed to identify articles describing therapeutic principles in the treatment of pediatric cough. An online survey of international pediatric cough experts was conducted, with questions on the definitions, diagnosis, treatment, and unmet needs in pediatric cough management. RESULTS: Cough guidelines have differing definitions of pediatric patients (≤12-18 years), acute pediatric cough (< 2-3 weeks), and chronic pediatric cough (> 4-8 weeks). Similarly, among 18 experts surveyed, definitions varied for pediatric patients (≤10-21 years), acute pediatric cough (< 3-5 days to < 6 weeks), and chronic pediatric cough (> 2-8 weeks). Guidelines generally do not recommend over-the-counter or prescription cough medicines in acute pediatric cough, due to lack of evidence. In the expert survey, participants had differing opinions on which medicines were most suitable for treating acute pediatric cough, and noted that effective treatments are lacking for cough-related pain and sleep disruption. Overall, guidelines and experts agreed that chronic pediatric cough requires diagnostic investigations to identify the underlying cough-causing disease and thereby to guide treatment. There are unmet needs for new effective and safe treatments for acute pediatric cough, and for randomized controlled trials of existing treatments. Safety is a particular concern in this vulnerable patient population. There is also a need for better understanding of the causes, phenotypes, and prevalence of pediatric cough, and how this relates to its diagnosis and treatment. CONCLUSIONS: Whereas pediatric cough guidelines largely align with regard to the diagnosis and treatment of chronic cough, there is limited evidence-based guidance for the management of acute cough. There is a need for harmonization of pediatric cough management, and the development of standard guidelines suitable for all regions and patient circumstances.
Asunto(s)
Tos , Humanos , Tos/diagnóstico , Tos/tratamiento farmacológico , Tos/etiología , Enfermedad Crónica , Encuestas y CuestionariosRESUMEN
BACKGROUND: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. METHODS: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. RESULTS: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. DISCUSSION: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown.
Asunto(s)
Medicina Integrativa , Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Estudios de Seguimiento , Humanos , Oncología Médica , Neoplasias/tratamiento farmacológico , Neoplasias/etiologíaRESUMEN
BACKGROUND: Gynecological cancer(s), including breast cancer patients in aftercare and survivors, need supportive strategies to cope with symptoms that are adapted to their individual needs and circumstances. Aromatherapy has potential to be such strategy, but (qualitative) empirical research taking users' own views into consideration about the potential and challenge of aromatherapy is lacking. PURPOSE: The purpose of the study is to gain insights from individualized aromatherapy as a supportive care treatment, regarding their use and evaluation by women with gynecological cancers in aftercare. METHODS: We conducted a study with a mixed-methods design, focused on qualitative research. Five essential oil products were given to 18 participants to apply individually over a 4-week period. After the intervention, qualitative semi-structured interviews were conducted. Further, we documented and assessed symptomatic burdens of the women (MYMOP2) before and after intervention quantitatively. RESULTS: Aromatherapy was customized by the participants according to their needs. It showed potential for relief of symptomatic burdens - especially nausea, peripheral neuropathy, pain, and sleep. Additionally, opportunities emerged to indirectly affect symptomatic burdens. These developed out of new coping strategies (e.g., sleep routines) or by combining with existing strategies (e.g., meditation). Furthermore, aromatherapy was successfully used to promote well-being and encourage mindfulness. CONCLUSION: Our findings demonstrated the potential of aromatherapy as a supportive treatment modality that can be used as a kind of toolbox. Challenges, such as individual odor aversions and intolerances, and limitations due to medication or illness should be considered in future aromatherapy research.
Asunto(s)
Aromaterapia , Neoplasias de la Mama , Humanos , Femenino , Aromaterapia/métodos , Cuidados Posteriores , Neoplasias de la Mama/terapia , Afecto , Adaptación PsicológicaRESUMEN
OBJECTIVE: To create an improved planning method for pediatric regional hyperthermia (RHT) using the SIGMA-30 applicator (SIGMA-30). MATERIALS AND METHODS: An electromagnetic model of SIGMA-30 was generated for use with the finite-difference time-domain (FDTD) method. Applying special MATLAB-based algorithms, voxel models of a pediatric patient with pelvic rhabdomyosarcoma were created from Computed-Tomography (CT) contours for use with the FDTD method and the finite-difference (FD) method capable of using either temperature-independent or temperature-dependent perfusion models for solving the Bioheat Transfer Equation (BHTE). Patient models were parametrized regarding, first, the positioning in the applicator, second, the absorbed power range and, third, different perfusion models, resulting in the so-called Parametrized Treatment Models (PTMs). A novel dedicated optimization procedure was developed based on quantitative comparison of numerical calculations against temperature and power measurements from two RHT therapies. RESULTS: Using measured data, a realistic absorbed power range in the patient model was estimated. Within this range, several FDTD and BHTE runs were performed and, applying the aforementioned optimization scheme, the best PTMs and perfusion models were identified for each therapy via a retrospective comparison with measurements in 14 temperature sensor positions: 5 in the tumor, 8 in rectum and one in bladder. CONCLUSION: A novel dedicated optimization procedure for identification of suitable patient-specific electromagnetic and thermal models, which can be used for improved patient planning, was developed and evaluated by comparison with treatment-derived measurements using SIGMA-30. The optimization procedure can be extended to other hyperthermia applicators and to other patient types, including adults.
Asunto(s)
Hipertermia Inducida , Neoplasias , Algoritmos , Niño , Humanos , Hipertermia , Neoplasias/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Understanding peoples' evaluations of their health care is important to ensure appropriate health-care services. OBJECTIVES: To understand what factors influence peoples' satisfaction with care and how interpersonal trust is established between doctors and cancer patients in Germany. DESIGN: A narrative interview study that included women with a diagnosis of breast cancer and men with a diagnosis of prostate cancer. A question-focused analysis was conducted. SETTING AND PARTICIPANTS: Interviewees were sought across Germany through self-help organizations, clinics, rehabilitation facilities, physicians and other health-care professionals, in order to develop modules on experiencing cancer for the website krankheitserfahrungen.de (illness experiences.de). RESULTS: Satisfaction was related to the perception of having a knowledgeable and trusted physician. Trust was developed through particular interactions in which 'medical expertise' and 'humaneness' were enacted by physicians. Humaneness represents the ability of physicians to personalize medical expertise and thereby to convey working in the individual's best interest and to treat the patient as an individual and unique human being. This was fostered through contextual and relational factors including among others setting, time, information transfer, respect, availability, profoundness, sensitivity and understanding. CONCLUSION: It was the ability to make oneself known to and know the patient in particular ways that allowed for satisfying care experiences by establishing interpersonal trust. This suggests the importance of conceptualizing the doctor-patient relationship as a fundamentally reciprocal human interaction of caregiving and care-receiving. At the core of the satisfying care experiences lies a doctor-patient relationship with a profoundly humane quality.
Asunto(s)
Neoplasias de la Próstata , Confianza , Humanos , Masculino , Satisfacción Personal , Relaciones Médico-Paciente , Neoplasias de la Próstata/terapia , Investigación CualitativaRESUMEN
Root hairs (RHs) develop from specialized epidermal trichoblast cells, whereas epidermal cells that lack RHs are known as atrichoblasts. The mechanism controlling RH cell fate is only partially understood. RH cell fate is regulated by a transcription factor complex that promotes the expression of the homeodomain protein GLABRA 2 (GL2), which blocks RH development by inhibiting ROOT HAIR DEFECTIVE 6 (RHD6). Suppression of GL2 expression activates RHD6, a series of downstream TFs including ROOT HAIR DEFECTIVE 6 LIKE-4 (RSL4) and their target genes, and causes epidermal cells to develop into RHs. Brassinosteroids (BRs) influence RH cell fate. In the absence of BRs, phosphorylated BIN2 (a Type-II GSK3-like kinase) inhibits a protein complex that regulates GL2 expression. Perturbation of the arabinogalactan peptide (AGP21) in Arabidopsis thaliana triggers aberrant RH development, similar to that observed in plants with defective BR signaling. We reveal that an O-glycosylated AGP21 peptide, which is positively regulated by BZR1, a transcription factor activated by BR signaling, affects RH cell fate by altering GL2 expression in a BIN2-dependent manner. Changes in cell surface AGP disrupts BR responses and inhibits the downstream effect of BIN2 on the RH repressor GL2 in root epidermis.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Regulación de la Expresión Génica de las Plantas , Glucógeno Sintasa Quinasa 3 , Mucoproteínas , Proteínas de Plantas , Raíces de Plantas/metabolismo , Proteínas QuinasasRESUMEN
PURPOSE: In the context of whole medical systems (WMSs), external applications are manual treatments that stem from complementary medicine and are performed by practitioners, nurses and caregivers through the application of interpersonal touch. These applications work via physiological, psychological and social processes and are intended for holistic healing. In integrative oncology, these applications are used to improve patients' wellbeing. The purpose of the review is to collect and compare research results concerning external applications from WMSs applied to patients with cancer. METHODS: We conducted a literature review to explore the effects of external applications on patients undergoing cancer treatment. Inclusion criteria were external applications from Anthroposophic Medicine, Traditional Chinese Medicine (TCM) and Ayurvedic Medicine, examined detached from the effect interdependencies of their respective WMSs. RESULTS: Searches identified 111 publications. Final inclusions were four Shiatsu studies (from TCM), supplemented by two case reports exploring anthroposophic external applications. The literature review suggests that external applications may improve patients' wellbeing during cancer treatment and are associated with physical and psychological effects that potentially enhance supportive cancer care. The number and quality of published studies in the field is limited. CONCLUSIONS: Future empirical investigations should assess the effectiveness and underlying effects in patients with cancer, adhere to a patient-tailored approach, and investigate the systemic complexity of touch-based applications from WMSs.
Asunto(s)
Terapias Complementarias , Salud Holística , Neoplasias , Tacto , Humanos , Terapias Complementarias/métodos , Atención a la Salud , Oncología Integrativa , Medicina Tradicional China , Neoplasias/psicología , Neoplasias/terapia , Tacto/fisiologíaRESUMEN
OBJECTIVE: Fever is a very common adaptive immune response in acute respiratory tract disorders during infancy. Antipyretic / analgesic drugs such as paracetamol (acetaminophen) are widely used to improve the comfort of the child but may cause medically unneeded antipyresis and rare but potentially serious side effects. We assess whether treatment with Pelargonium sidoides extract EPs 7630 reduces the administration of paracetamol in children with acute tonsillopharyngitis (ATP) or acute bronchitis (AB). DESIGN: Meta-analysis of randomised, placebo-controlled clinical trials. METHODS: We searched clinical trial registries (ISRCTN, ClinicalTrials.gov ) and medical literature (MEDLINE, EMBASE), for randomised, placebo-controlled trials investigating the administration of EPs 7630 to children with ATP or AB and reporting the co-administration of paracetamol. Based on the individual participant data of the eligible trials, study populations were characterized according to sex and age, and meta-analyses were performed for cumulative paracetamol use and ability to attend school at treatment end. RESULTS: Six trials including a total of 523 children aged 6-10 years (EPs 7630: 265; placebo: 258) and suffering from non-ß-hemolytic streptococcal ATP (3 trials) or from AB (3 trials) were identified and eligible. Children received EPs 7630 or placebo for 6 (ATP) or 7 days (AB). Compared to placebo, EPs 7630 reduced the cumulative dose of paracetamol in 5 out of the 6 trials, by an average of 244 mg (Hedges' g; - 0.28; 95% confidence interval: [- 0.53; - 0.02]; p < 0.03). At treatment end, 30.2% (EPs 7630) and 74.4% (placebo) of the children were still unable to attend school (risk ratio: 0.43; 95% confidence interval: [0.29; 0.65]; p < 0.001). CONCLUSIONS: In children aged 6-10 years with AB or ATP, EPs 7630 alleviated the symptom burden and accelerated recovery. Although EPs 7630 has no known antipyretic effect, concomitant use of paracetamol was reduced.
Asunto(s)
Acetaminofén/uso terapéutico , Fiebre/tratamiento farmacológico , Recuperación de la Función , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedad Aguda , Analgésicos no Narcóticos/uso terapéutico , Niño , Fiebre/etiología , Humanos , Infecciones del Sistema Respiratorio/complicaciones , Factores de TiempoRESUMEN
Fasciclin-like arabinogalactan proteins (FLAs) are involved in numerous important functions in plants but the relevance of their complex structure to physiological function and cellular fate is unresolved. Using a fully functional fluorescent version of Arabidopsis thaliana FLA4 we show that this protein is localized at the plasma membrane as well as in endosomes and soluble in the apoplast. FLA4 is likely to be GPI-anchored, is highly N-glycosylated and carries two O-glycan epitopes previously associated with arabinogalactan proteins. The activity of FLA4 was resistant against deletion of the amino-proximal fasciclin 1 domain and was unaffected by removal of the GPI-modification signal, a highly conserved N-glycan or the deletion of predicted O-glycosylation sites. Nonetheless these structural changes dramatically decreased endoplasmic reticulum (ER)-exit and plasma membrane localization of FLA4, with N-glycosylation acting at the level of ER-exit and O-glycosylation influencing post-secretory fate. We show that FLA4 acts predominantly by molecular interactions involving its carboxy-proximal fasciclin 1 domain and that its amino-proximal fasciclin 1 domain is required for stabilization of plasma membrane localization. FLA4 functions as a soluble glycoprotein via its carboxy-proximal Fas1 domain and its normal cellular trafficking depends on N- and O-glycosylation.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Moléculas de Adhesión Celular/metabolismo , Arabidopsis/citología , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Moléculas de Adhesión Celular/genética , Retículo Endoplásmico/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Glicosilación , Proteínas Luminiscentes , Mucoproteínas/genética , Mucoproteínas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/citología , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Polisacáridos/metabolismo , Dominios Proteicos , Transporte de Proteínas , Proteínas Recombinantes de FusiónRESUMEN
The Fasciclin 1 (FAS1) domain is an ancient structural motif in extracellular proteins present in all kingdoms of life and particularly abundant in plants. The FAS1 domain accommodates multiple interaction surfaces, enabling it to bind different ligands. The frequently observed tandem FAS1 arrangement might both positively and negatively regulate ligand binding. Additional protein domains and post-translational modifications are partially conserved between different evolutionary clades. Human FAS1 family members are associated with multiple aspects of health and disease. At the cellular level, mammalian FAS1 proteins are implicated in extracellular matrix structure, cell to extracellular matrix and cell to cell adhesion, paracrine signaling, intracellular trafficking and endocytosis. Mammalian FAS1 proteins bind to the integrin family of receptors and to protein and carbohydrate components of the extracellular matrix. FAS1 protein encoding plant genes exert effects on cellulosic and non-cellulosic cell wall structure and cellular signaling but to establish the modes of action for any plant FAS1 protein still requires biochemical experimentation. In fungi, eubacteria and archaea, the differential presence of FAS1 proteins in closely related organisms and isolated biochemical data suggest functions in pathogenicity and symbiosis. The inter-kingdom comparison of FAS1 proteins suggests that molecular mechanisms mediating interactions between cells and their environment may have evolved at the earliest known stages of evolution.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Membrana Celular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Adhesión Celular , Moléculas de Adhesión Celular/química , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular Neuronal/química , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/química , Proteínas de la Matriz Extracelular/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glicosilación , Humanos , Familia de Multigenes , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Relación Estructura-ActividadRESUMEN
BACKGROUND: Osteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscum album L.) are used in complementary cancer treatment. These commercial extracts are water-based and do not include water-insoluble compounds such as triterpenic acids. However, both hydrophilic and hydrophobic triterpenic acids possess anti-cancer properties. In this study, a whole mistletoe extract viscumTT re-created by combining an aqueous extract (viscum) and a triterpene extract (TT) was tested for its anti-cancer potential in osteosarcoma. METHODS: Two osteosarcoma cell lines were treated with three different mistletoe extracts viscum, TT and viscumTT to compare their apoptotic potential. For this purpose, annexin/PI staining and caspase-3, -8 and -9 activity were investigated by flow cytometry. To determine the mechanism of action, alterations in expression of inhibitors of apoptosis (IAPs) were detected by western blot. Apoptosis induction by co-treatment of viscum, TT and viscumTT with doxorubicin, etoposide and ifosfamide was examined by flow cytometry. RESULTS: In vitro as well as ex vivo, the whole mistletoe extract viscumTT led to strong inhibition of proliferation and synergistic apoptosis induction in osteosarcoma cells. In the investigations of mechanism of action, inhibitors of apoptosis such as XIAP, BIRC5 and CLSPN showed a clear down-regulation after viscumTT treatment. In addition, co-treatment with doxorubicin, etoposide and ifosfamide further enhanced apoptosis induction, also synergistically. CONCLUSION: ViscumTT treatment results in synergistic apoptosis induction in osteosarcoma cells in vitro and ex vivo. Additionally, conventional standard chemotherapeutic drugs such as doxorubicin, etoposide and ifosfamide were able to dramatically enhance apoptosis induction. These results promise a high potential of viscumTT as an additional adjuvant therapy approach for osteosarcoma.
Asunto(s)
Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Proteínas Inhibidoras de la Apoptosis/genética , Osteosarcoma/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Triterpenos/administración & dosificación , Viscum album/química , Proliferación Celular/efectos de los fármacos , Niño , Doxorrubicina/administración & dosificación , Sinergismo Farmacológico , Quimioterapia Combinada , Etopósido/administración & dosificación , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Masculino , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/fisiopatología , Survivin , Células Tumorales Cultivadas , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismoRESUMEN
BACKGROUND: In Germany, about 1,800 new cases of pediatric cancer under 15 years of age are diagnosed each year and survival rates approach 80%. Although treatment is covered by health insurance and is thus available for all patients at no cost, treatment refusal and treatment discontinuation have been observed. However, no data providing numbers and outcomes for developed countries have been published thus far. PROCEDURE: A questionnaire-based survey was performed among German pediatric oncology centers to ascertain the number of treatment refusals among pediatric patients who were diagnosed between January 2008 and December 2009 in Germany. RESULTS: Questionnaires from 70 of 73 centers were available, and of these 13 centers reported a total of 15 cases of treatment refusal or discontinuation within this 2-year period. Five of the 15 patients died, 7 of 15 were still alive, and the current status of 3 of 15 patients was unknown. Diseases were heterogeneous. Six of the 15 parents refused treatment for their children initially, 8 of 15 discontinued during the course of treatment. Five patients were treated after parental custody had been withdrawn due to the lack of compliance. All these five patients survived. Parents' reasons given for refusal or discontinuation of treatment were related to personal health beliefs and coping strategies. CONCLUSIONS: Although treatment refusal or discontinuation is rare, it is accompanied by a high mortality rate. Parents' personal health beliefs play a primary role in treatment refusal or discontinuation in Germany. This emphasizes the importance of sustaining a functioning and mutually communicative physician-parent-patient relationship.
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Neoplasias/terapia , Negativa del Paciente al Tratamiento , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasias/mortalidad , Padres , Relaciones Médico-Paciente , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Arabidopsis EARLI-type hybrid proline-rich proteins (HyPRPs) consist of a putative N-terminal secretion signal, a proline-rich domain (PRD), and a characteristic eight-cysteine-motif (8-CM). They have been implicated in biotic and abiotic stress responses. AZI1 is required for systemic acquired resistance and it has recently been identified as a target of the stress-induced mitogen-activated protein kinase MPK3. AZI1 gel migration properties strongly indicate AZI1 to undergo major post-translational modifications. These occur in a stress-independent manner and are unrelated to phosphorylation by MAPKs. As revealed by transient expression of AZI1 in Nicotiana benthamiana and Tropaeolum majus, the Arabidopsis protein is similarly modified in heterologous plant species. Proline-rich regions, resembling arabinogalactan proteins point to a possible proline hydroxylation and subsequent O-glycosylation of AZI1. Consistently, inhibition of prolyl hydroxylase reduces its apparent protein size. AZI1 secretion was examined using Arabidopsis protoplasts and seedling exudates. Employing Agrobacterium-mediated leaf infiltration of N. benthamiana, we attempted to assess long-distance movement of AZI1. In summary, the data point to AZI1 being a partially secreted protein and a likely new member of the group of hydroxyproline-rich glycoproteins. Its dual location suggests AZI1 to exert both intra- and extracellular functions.
Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/genética , Procesamiento Proteico-Postraduccional , Agrobacterium tumefaciens/genética , Agrobacterium tumefaciens/metabolismo , Secuencia de Aminoácidos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Glicosilación , Hidroxiprolina/metabolismo , Datos de Secuencia Molecular , Hojas de la Planta/metabolismo , Transporte de Proteínas , Protoplastos/metabolismo , Plantones/genética , Plantones/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , TransfecciónRESUMEN
Interactions between cell wall polymers are critical for establishing cell wall integrity and cell-cell adhesion. Here, we exploit the Arabidopsis (Arabidopsis thaliana) seed coat mucilage system to examine cell wall polymer interactions. On hydration, seeds release an adherent mucilage layer strongly attached to the seed in addition to a nonadherent layer that can be removed by gentle agitation. Rhamnogalacturonan I (RG I) is the primary component of adherent mucilage, with homogalacturonan, cellulose, and xyloglucan constituting minor components. Adherent mucilage contains rays composed of cellulose and pectin that extend above the center of each epidermal cell. CELLULOSE SYNTHASE5 (CESA5) and the arabinogalactan protein SALT-OVERLY SENSITIVE5 (SOS5) are required for mucilage adherence through unknown mechanisms. SOS5 has been suggested to mediate adherence by influencing cellulose biosynthesis. We, therefore, investigated the relationship between SOS5 and CESA5. cesa5-1 seeds show reduced cellulose, RG I, and ray size in adherent mucilage. In contrast, sos5-2 seeds have wild-type levels of cellulose but completely lack adherent RG I and rays. Thus, relative to each other, cesa5-1 has a greater effect on cellulose, whereas sos5-2 mainly affects pectin. The double mutant cesa5-1 sos5-2 has a much more severe loss of mucilage adherence, suggesting that SOS5 and CESA5 function independently. Double-mutant analyses with mutations in MUCILAGE MODIFIED2 and FLYING SAUCER1 that reduce mucilage release through pectin modification suggest that only SOS5 influences pectin-mediated adherence. Together, these findings suggest that SOS5 mediates adherence through pectins and does so independently of but in concert with cellulose synthesized by CESA5.
RESUMEN
BACKGROUND AND AIMS: The putative FASCICLIN-LIKE ARABINOGALACTAN PROTEIN 4 (At-FLA4) locus of Arabidopsis thaliana has previously been shown to be required for the normal growth of wild-type roots in response to moderately elevated salinity. However, the genetic and physiological pathway that connects At-FLA4 and normal root growth remains to be elucidated. METHODS: The radial swelling phenotype of At-fla4 was modulated with growth regulators and their inhibitors. The relationship of At-FLA4 to abscisic acid (ABA) signalling was analysed by probing marker gene expression and the observation of the At-fla4 phenotype in combination with ABA signalling mutants. KEY RESULTS: Application of ABA suppresses the non-redundant role of At-FLA4 in the salt response. At-FLA4 positively regulates the response to low ABA concentration in roots and is required for the normal expression of ABA- and abiotic stress-induced genes. The At-fla4 phenotype is enhanced in the At-abi4 background, while two genetic suppressors of ABA-induced gene expression are required for salt oversensitivity of At-fla4. Salt oversensitivity in At-fla4 is suppressed by the CYP707A inhibitor abscinazole E2B, and salt oversensitivity in At-fla4 roots is phenocopied by chemical inhibition of ABA biosynthesis. CONCLUSIONS: The predicted lipid-anchored glycoprotein At-FLA4 positively regulates cell wall biosynthesis and root growth by modulating ABA signalling.
Asunto(s)
Ácido Abscísico/metabolismo , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Mucoproteínas/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Transducción de Señal , Arabidopsis/efectos de los fármacos , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pared Celular/metabolismo , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Modelos Genéticos , Mucoproteínas/metabolismo , Mutación , Fenotipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Plantas Modificadas Genéticamente , Cloruro de Sodio/farmacología , Estrés Fisiológico , Triazoles/farmacologíaRESUMEN
Background: The holistic health and wellness Kneipp concept, has a long tradition in Europe with demonstrated health benefits. Based on the five elements of the Kneipp concept, kindergartens in and around Germany are used to certify "Kneipp Kindergartens" that practice regular Kneipp applications and activities: cold water applications, exercise, nutrition, herbs and mind-body interventions. Little is known about the potential health benefits for children, however. This study protocol describes our study design and intervention of the Kita Kneipp Study to investigate the effect of the Kneipp concept on kindergarten children aged 2-6 years. Methods and design: The Kita Kneipp Study, registered with the German Clinical Trial Register (DRKS-ID: DRKS00029275), is a confirmatory, mixed-method, two-armed, waitlist, clinical, cluster randomized controlled trial (RCT). Kindergartens in Berlin, Germany that would like to implement the Kneipp concept into their facility will be recruited and randomized to the intervention or control group. Changes in the number of kindergarten sick days will be the primary outcome measure. Kindergarten attendance and reason for absence including illness will be collected on a weekly basis at two time points for 6 weeks from the parents and kindergarten directors: baseline and 1 year after baseline. Secondary outcomes will measure cold symptoms through the Common Cold Questionnaire (CCQ) and National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Scales describing gastroenterological-based symptoms Kindergarten educator sick days will be aggregately reported for the same time period. Kneipp concept activities will be recorded on a weekly basis over the one-year intervention period. To understand the experience of Kneipp concept implementation and possible changes in the kindergarten, expert interviews will be conducted with intervention kindergarten educators and focused ethnographies will be planned to observe and analyze the intervention activities. Discussion: This mixed method study design has potential to help identify if the Kneipp concept can be used for salutogenic purposes among young children and provide insights and experience of the implementation and practicing a holistic health and wellness concept in a kindergarten setting.