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AIM: To identify short-term effects of botulinum neurotoxin type A (BoNT) injections on gait and clinical impairments, in children with spastic cerebral palsy (CP), based on baseline gait pattern-specific subgroups. METHOD: Short-term effects of BoNT injections in the medial hamstrings and gastrocnemius were defined in a retrospective convenience sample of 117 children with CP (median age: 6 years 4 months; GMFCS I/II/III: 70/31/16; unilateral/bilateral: 56/61) who had received gait analyses before and 2 months post-BoNT. First, baseline gait patterns were classified. Statistical and meaningful changes were calculated between pre- and post-BoNT lower limb sagittal plane kinematic waveforms, the gait profile score, and non-dimensional spatiotemporal parameters for the entire sample and for pattern-specific subgroups. These gait waveforms per CP subgroup at pre- and post-BoNT were also compared to typically developing gait and composite scores for spasticity, weakness, and selectivity were compared between the two conditions. RESULTS: Kinematic improvements post-BoNT were identified at the ankle and knee for the entire sample, and for subgroups with apparent equinus and jump gait. Limbs with baseline patterns of dropfoot and to a lesser extent true equinus showed clear improvements only at the ankle. In apparent equinus, jump gait, and dropfoot, spasticity improved post-BoNT, without leading to increased weakness or diminished selectivity. Compared to typical gait, knee and hip motion improved in the crouch gait subgroup post-BoNT. CONCLUSION: This comprehensive analysis highlighted the importance of investigating BoNT effects on gait and clinical impairments according to baseline gait patterns. These findings may help identify good treatment responders.
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Toxinas Botulínicas Tipo A , Parálisis Cerebral , Fármacos Neuromusculares , Humanos , Parálisis Cerebral/tratamiento farmacológico , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/complicaciones , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/farmacología , Toxinas Botulínicas Tipo A/uso terapéutico , Niño , Masculino , Femenino , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/farmacología , Estudios Retrospectivos , Preescolar , Fenómenos Biomecánicos/efectos de los fármacos , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Músculo Esquelético/fisiopatología , Músculo Esquelético/efectos de los fármacos , Adolescente , Resultado del Tratamiento , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Espasticidad Muscular/etiología , Marcha/efectos de los fármacos , Marcha/fisiologíaRESUMEN
BACKGROUND: With increasing survival rates of adolescents and young adults (AYAs) with breast cancer, health-related quality of life (HRQoL) becomes more important. An important aspect of HRQoL is sexual QoL. This study examined long-term sexual QoL of AYA breast cancer survivors, compared sexual QoL scores with that of other AYA cancer survivors, and identified factors associated with long-term sexual QoL of AYA breast cancer survivors. MATERIALS AND METHODS: Data of the SURVAYA study were utilized for secondary analyses. Sexual QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). Descriptive statistics were used to describe sexual QoL of AYA cancer survivors. Linear regression models were constructed to examine the effect of cancer type on sexual QoL and to identify factors associated with sexual QoL. RESULTS: Of the 4010 AYA cancer survivors, 944 had breast cancer. Mean sexual QoL scores of AYA breast cancer survivors ranged from 34.5 to 60.0 for functional domains and from 25.2 to 41.5 for symptom-orientated domains. AYA breast cancer survivors reported significantly lower sexual QoL compared to AYA survivors of other cancer types on all domains. Age, time since diagnosis, relationship status, educational level, chemotherapy, hormonal therapy, breast surgery, body image, and coping were associated with sexual QoL of AYA breast cancer survivors. CONCLUSIONS: AYA breast cancer survivors experience decreased sexual QoL in the long term (5-20 years) after diagnosis and worse score compared to AYA survivors of other cancer types, indicating a clear need to invest in supportive care interventions for those at risk, to enhance sexual well-being.
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Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Adolescente , Adulto Joven , Femenino , Neoplasias de la Mama/terapia , Calidad de Vida , Sobrevivientes , MamaRESUMEN
PURPOSE: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. METHODS: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. RESULTS: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p < 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p < 0.05). CONCLUSION: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/cirugía , Estudios Longitudinales , Calidad de Vida/psicología , Metástasis Linfática , Axila/cirugía , Estudios de CohortesRESUMEN
BACKGROUND: In response to noxious stimulation, pupillary dilation reflex (PDR) occurs even in anaesthetized patients. The aim of the study was to evaluate the ability of pupillometry with an automated increasing stimulus intensity to monitor intraoperative opioid administration. METHODS: Thirty-four patients undergoing elective surgery were enrolled. Induction by propofol anaesthesia was increased progressively until the sedation depth criteria (SeD) were attained. Subsequently, a first dynamic pupil measurement was performed by applying standardized nociceptive stimulation (SNS). A second PDR evaluation was performed when remifentanil reached a target effect-site concentration. Automated infrared pupillometry was used to determine PDR during nociceptive stimulations generating a unique pupillary pain index (PPI). Vital signs were measured. RESULTS: After opioid administration, anaesthetized patients required a higher stimulation intensity (57.43 mA vs 32.29 mA, P < .0005). Pupil variation in response to the nociceptive stimulations was significantly reduced after opioid administration (8 mm vs 28 mm, P < .0005). The PPI score decreased after analgesic treatment (8 vs 2, P < .0005), corresponding to a 30% decrease. The elicitation of PDR by nociceptive stimulation was performed without changes in vital signs before (HR 76 vs 74/min, P = .09; SBP 123 vs 113 mm Hg, P = .001) and after opioid administration (HR 63 vs 62/min, P = .4; SBP 98.66 vs 93.77 mm Hg, P = .032). CONCLUSIONS: During propofol anaesthesia, pupillometry with the possibility of low-intensity standardized noxious stimulation via PPI protocol can be used for PDR assessment in response to remifentanil administration.
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Aneurisma de la Aorta Torácica/genética , Disección Aórtica/genética , Proteínas de Unión al Calcio/genética , Quinasa de Cadena Ligera de Miosina/genética , Anciano , Disección Aórtica/fisiopatología , Aneurisma de la Aorta Torácica/fisiopatología , Codón sin Sentido/genética , Femenino , Haploinsuficiencia/genética , Humanos , Masculino , Anamnesis , Persona de Mediana Edad , LinajeRESUMEN
Uterine smooth muscle tumors of uncertain malignant potential, or STUMP, form a rare group of tumors that fall neither into the benign nor malignant categories. Two cases are reported, describing diagnosis, known prognostic factors, and therapy. In contrast to leiomyomas and leiomyosarcomas, many uncertainties still exist concerning prognosis and postoperative management of STUMP, because of their rarity. Diagnosis is usually not made preoperatively, but by postoperative anatomo-pathological examination. There are histological and immunohistochemical factors that could be associated with a worse prognosis, but scientific evidence is insufficient. Most cases show a low risk of recurrence, although individual risk is unpredictable. Recurrences mostly occur after a long disease-free interval. A conservative approach with strict long-term clinical follow-up is therefore indicated. Further research must be conducted to identify surgical procedures that have a higher risk for recurrence. After a laparoscopy, where the specimen was morcellated, the possibility of peritoneal spread and the difficulty in examining section margins, need to be taken into account. Further treatment therefore needs to be individualized.
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Tumor de Músculo Liso/patología , Neoplasias Uterinas/patología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Pronóstico , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapiaRESUMEN
Facial trauma. Patients with facial trauma must be assessed in a systematic way so as to avoid missing any injury. Severe and disfiguring facial injuries can be distracting. However, clinicians must first focus on the basics of trauma care, following the Advanced Trauma Life Support (ATLS) system of care. Maxillofacial trauma occurs in a significant number of severely injured patients. Life- and sight-threatening injuries must be excluded during the primary and secondary surveys. Special attention must be paid to sight-threatening injuries in stabilized patients through early referral to an appropriate specialist or the early initiation of emergency care treatment. The gold standard for the radiographic evaluation of facial injuries is computed tomography (CT) imaging. Nasal fractures are the most frequent isolated facial fractures. Isolated nasal fractures are principally diagnosed through history and clinical examination. Closed reduction is the most frequently performed treatment for isolated nasal fractures, with a fractured nasal septum as a predictor of failure. Ear, nose and throat surgeons, maxillofacial surgeons and ophthalmologists must all develop an adequate treatment plan for patients with complex maxillofacial trauma.
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Traumatismos Faciales/diagnóstico , Traumatismos Faciales/cirugía , Algoritmos , Antibacterianos/uso terapéutico , Diagnóstico por Imagen , Servicios Médicos de Urgencia , Huesos Faciales/diagnóstico por imagen , Huesos Faciales/lesiones , Huesos Faciales/cirugía , Fijación de Fractura , Fracturas Óseas/diagnóstico , Fracturas Óseas/cirugía , Humanos , Anamnesis , Examen Físico , Tiempo de TratamientoRESUMEN
UNLABELLED: The plant pathogen Ralstonia solanacearum possesses two genes encoding a trehalose-6-phosphate synthase (TPS), an enzyme of the trehalose biosynthetic pathway. One of these genes, named ripTPS, was found to encode a protein with an additional N-terminal domain which directs its translocation into host plant cells through the type 3 secretion system. RipTPS is a conserved effector in the R. solanacearum species complex, and homologues were also detected in other bacterial plant pathogens. Functional analysis of RipTPS demonstrated that this type 3 effector synthesizes trehalose-6-phosphate and identified residues essential for this enzymatic activity. Although trehalose-6-phosphate is a key signal molecule in plants that regulates sugar status and carbon assimilation, the disruption of ripTPS did not alter the virulence of R. solanacearum on plants. However, heterologous expression assays showed that this effector specifically elicits a hypersensitive-like response on tobacco that is independent of its enzymatic activity and is triggered by the C-terminal half of the protein. Recognition of this effector by the plant immune system is suggestive of a role during the infectious process. IMPORTANCE: Ralstonia solanacearum, the causal agent of bacterial wilt disease, infects more than two hundred plant species, including economically important crops. The type III secretion system plays a major role in the pathogenicity of this bacterium, and approximately 70 effector proteins have been shown to be translocated into host plant cells. This study provides the first description of a type III effector endowed with a trehalose-6-phosphate synthase enzymatic activity and illustrates a new mechanism by which the bacteria may manipulate the plant metabolism upon infection. In recent years, trehalose-6-phosphate has emerged as an essential signal molecule in plants, connecting plant metabolism and development. The finding that a bacterial pathogen could induce the production of trehalose-6-phosphate in plant cells further highlights the importance of this metabolite in multiple aspects of the molecular physiology of plants.
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Proteínas Bacterianas/metabolismo , Plantas/metabolismo , Plantas/microbiología , Ralstonia solanacearum/metabolismo , Fosfatos de Azúcar/metabolismo , Trehalosa/análogos & derivados , Factores de Virulencia/metabolismo , Plantas/inmunología , Transporte de Proteínas , Trehalosa/metabolismoRESUMEN
Plant cells contain two organelles originally derived from endosymbiotic bacteria: mitochondria and plastids. Their endosymbiotic origin explains why these organelles contain their own DNA, nonetheless only a few dozens of genes are actually encoded by these genomes. Many of the other genes originally present have been transferred to the nuclear genome of the host, the product of their expression being targeted back to the corresponding organelle. Although targeting of proteins to mitochondria and chloroplasts is generally highly specific, an increasing number of examples have been discovered where the same protein is imported into both organelles. The object of this review is to compare and discuss these examples in order to try and identify common features of dual-targeted proteins. The study helps throw some light on the factors determining organelle targeting specificity, and suggests that dual-targeted proteins may well be far more common than once thought.
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Cloroplastos/metabolismo , Mitocondrias/metabolismo , Proteínas de Plantas/metabolismo , Marcación de Gen , Proteínas de Plantas/genética , Transporte de ProteínasRESUMEN
Transcripts of typical dicot plant plastid genes undergo C-->U RNA editing at approximately 30 locations, but there is no consensus sequence surrounding the C targets of editing. The cis-acting elements required for editing of the C located at tobacco rpoB editing site II were investigated by introducing translatable chimeric minigenes containing sequence -20 to +6 surrounding the C target of editing. When the -20 to +6 sequence specified by the homologous region present in the black pine chloroplast genome was incorporated, virtually no editing of the transcripts occurred in transgenic tobacco plastids. Nucleotides that differ between the black pine and tobacco sequence were tested for their role in C-->U editing by designing chimeric genes containing one or more of these divergent nucleotides. Surprisingly, the divergent nucleotide that had the strongest negative effect on editing of the minigene transcript was located -20 nt 5' to the C target of editing. Expression of transgene transcripts carrying the 27 nt sequence did not affect the editing extent of the endogenous rpoB transcripts, even though the chimeric transcripts were much more abundant than those of the endogenous gene. In plants carrying a 93 nt rpoB editing site sequence, transgene transcripts accumulated to a level three times greater than transgene transcripts in the plants carrying the 27 nt rpoB editing sites and resulted in editing of the endogenous transcripts from 100 to 50%. Both a lower affinity of the 27 nt site for a trans-acting factor and lower abundance of the transcript could explain why expression of minigene transcripts containing the 27 nt sequence did not affect endogenous editing.
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Cloroplastos/metabolismo , ADN de Cloroplastos/genética , Edición de ARN , ARN de Planta/metabolismo , Secuencia de Bases , Sitios de Unión/genética , Cloroplastos/genética , ADN Complementario/genética , ADN Complementario/metabolismo , ARN Polimerasas Dirigidas por ADN , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Proteínas de Plantas/genética , Plantas Tóxicas , ARN de Planta/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico , Nicotiana/genética , Transcripción Genética , Transformación GenéticaRESUMEN
In plant mitochondria, some of the tRNAs are encoded by the mitochondrial genome and resemble their prokaryotic counterparts, whereas the remaining tRNAs are encoded by the nuclear genome and imported from the cytosol. Generally, mitochondrial isoacceptor tRNAs all have the same genetic origin. One known exception to this rule is the group of tRNA(Gly) isoacceptors in dicotyledonous plants. A mitochondrion-encoded tRNA(Gly) and at least one nucleus-encoded tRNA(Gly) coexist in the mitochondria of these plants, and both are required to allow translation of all four GGN glycine codons. We have taken advantage of this atypical situation to address the problem of tRNA/aminoacyl-tRNA synthetase coevolution in plants. In this work, we show that two different nucleus-encoded glycyl-tRNA synthetases (GlyRSs) are imported into Arabidopsis thaliana and Phaseolus vulgaris mitochondria. The first one, GlyRS-1, is similar to human or yeast glycyl-tRNA synthetase, whereas the second, GlyRS-2, is similar to Escherichia coli glycyl-tRNA synthetase. Both enzymes are dual targeted, GlyRS-1 to mitochondria and to the cytosol and GlyRS-2 to mitochondria and chloroplasts. Unexpectedly, GlyRS-1 seems to be active in the cytosol but inactive in mitochondrial fractions, whereas GlyRS-2 is likely to glycylate both the organelle-encoded tRNA(Gly) and the imported tRNA(Gly) present in mitochondria.
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Arabidopsis/enzimología , Fabaceae/enzimología , Glicina-ARNt Ligasa/metabolismo , Plantas Medicinales , Secuencia de Aminoácidos , Secuencia de Bases , Western Blotting , Cromatografía Liquida , ADN de Plantas , Escherichia coli/genética , Glicina-ARNt Ligasa/genética , Mitocondrias/enzimología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Fracciones Subcelulares/enzimología , Especificidad por SustratoRESUMEN
Two cysteinyl-tRNA synthetases (CysRS) and four asparaginyl-tRNA synthetases (AsnRS) from Arabidopsis thaliana were characterized from genome sequence data, EST sequences, and RACE sequences. For one CysRS and one AsnRS, sequence alignments and prediction programs suggested the presence of an N-terminal organellar targeting peptide. Transient expression of these putative targeting sequences joined to jellyfish green fluorescent protein (GFP) demonstrated that both presequences can efficiently dual-target GFP to mitochondria and plastids. The other CysRS and AsnRSs lack targeting sequences and presumably aminoacylate cytosolic tRNAs. Phylogenetic analysis suggests that the four AsnRSs evolved by repeated duplication of a gene transferred from an ancestral plastid and that the CysRSs also arose by duplication of a transferred organelle gene (possibly mitochondrial). These case histories are the best examples to date of capture of organellar aminoacyl-tRNA synthetases by the cytosolic protein synthesis machinery.
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Aminoacil-ARNt Sintetasas/genética , Arabidopsis/genética , Aspartato-ARNt Ligasa , Duplicación de Gen , Aminoacil-ARN de Transferencia , Secuencia de Aminoácidos , Aminoacil-ARNt Sintetasas/química , Animales , Arabidopsis/enzimología , Secuencia de Bases , Cartilla de ADN , ADN Complementario , Humanos , Datos de Secuencia Molecular , Orgánulos/enzimología , Filogenia , Homología de Secuencia de AminoácidoAsunto(s)
Secuencias de Aminoácidos , Proteínas Potenciadoras de Unión a CCAAT , Proteínas de Plantas/química , Proteínas de Saccharomyces cerevisiae , Secuencia de Aminoácidos , Arabidopsis/química , Arabidopsis/genética , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales , Datos de Secuencia Molecular , Orgánulos/metabolismo , Factores de Iniciación de Péptidos , Proteínas de Plantas/metabolismo , Proteínas/química , Homología de Secuencia de Aminoácido , Programas Informáticos , Factores de Transcripción/química , Factores de Transcripción/metabolismoRESUMEN
Choreoathetosis is a major clinical feature in only a small number of hereditary neurological disorders. We define a new X-linked syndrome with a unique clinical picture characterized by mild mental retardation, choreoathetosis, and abnormal behavior. We mapped the disease in a four-generation pedigree to chromosome Xp11 by linkage analysis and defined a candidate region containing a number of genes possibly involved in neuronal signaling, including a potassium channel gene and a neuronal G protein-coupled receptor.