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BACKGROUND AND HYPOTHESIS: Dysregulated energy metabolism is a recently discovered key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Cystic cells depend on glucose and are poorly able to use other energy sources such as ketone bodies. Raising ketone body concentration reduced disease progression in animal models of polycystic kidney diseases. Therefore, we hypothesized that higher endogenous plasma beta-hydroxybutyrate concentrations are associated with reduced disease progression in patients with ADPKD. METHODS: We analyzed data from 670 patients with ADPKD participating in the DIPAK cohort, a multi-center prospective observational cohort study. Beta-hydroxybutyrate was measured at baseline using nuclear magnetic resonance spectroscopy. Participants were excluded if they had type 2 diabetes, were using disease-modifying drugs (e.g. tolvaptan, somatostatin analogs), were not fasting, or had missing beta-hydroxybutyrate levels, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations. RESULTS: Of the participants, 61% were female, with an age of 47.3 ± 11.8 years, a height-adjusted total kidney volume (htTKV) of 834 (IQR 495-1327) ml/m, and an estimated glomerular filtration rate (eGFR) of 63.3 ± 28.9 mL/min/1.73m2. The median concentration of beta-hydroxybutyrate was 94 (IQR 68-147) µmol/L. Cross-sectionally, beta-hydroxybutyrate was neither associated with eGFR nor with htTKV. Longitudinally, beta-hydroxybutyrate was positively associated with eGFR slope (B = 0.35 ml/min/1.73m2 (95% CI 0.09 to 0.61), p = 0.007), but not with kidney growth. After adjustment for potential confounders, every doubling in beta-hydroxybutyrate concentration was associated with an improvement in the annual rate of eGFR by 0.33 ml/min/1.73m2 (95% CI 0.09 to 0.57, p = 0.008). CONCLUSION: These observational analyses support the hypothesis that interventions that raise beta-hydroxybutyrate concentration could reduce the rate of kidney function decline in patients with ADPKD.
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OBJECTIVES: Evidence regarding placental function in pregnancies complicated by confined placental mosaicism (CPM) is conflicting. We aimed to compare placental function between CPM and non-CPM pregnancies prenatally and at birth. A secondary objective was to evaluate the relationship between placental function and chromosomal subtype of CPM. METHODS: This was a retrospective study of pregnancies with CPM and control pregnancies delivered at a tertiary hospital in Denmark between 2014 and 2017. Placental volume and placental transverse relaxation time (T2*) were estimated on magnetic resonance imaging (MRI), fetal weight and uterine artery pulsatility index (UtA-PI) were estimated on ultrasound and fetoplacental ratio was assessed on MRI and at birth. These estimates of placental function were adjusted for gestational age and compared between groups using the Wilcoxon rank-sum test. Within the group of CPM pregnancies, measures of placental function were compared between those at high risk (chromosome numbers 2, 3, 7, 13 and 16) and those at low risk (chromosome numbers 5, 18 and 45X). RESULTS: A total of 90 pregnancies were included, of which 12 had CPM and 78 were controls. MRI and ultrasound examinations were performed at a median gestational age of 32.6 weeks (interquartile range, 24.7-35.3 weeks). On MRI assessment, CPM placentae were characterized by a lower placental T2* Z-score (P = 0.004), a lower fetoplacental ratio (P = 0.03) and a higher UtA-PI Z-score (P = 0.03), compared with non-CPM placentae. At birth, the fetoplacental ratio was significantly lower (P = 0.02) and placental weight Z-score was higher (P = 0.01) in CPM pregnancies compared with non-CPM pregnancies. High-risk CPM pregnancies showed a reduced placental T2* Z-score (P = 0.003), lower birth-weight Z-score (P = 0.041), earlier gestational age at delivery (P = 0.019) and higher UtA-PI Z-score (P = 0.028) compared with low-risk CPM pregnancies. Low-risk CPM pregnancies did not differ in any of these parameters from non-CPM pregnancies. CONCLUSIONS: CPM pregnancies are characterized by an enlarged and dysfunctional placenta. Placental function was highly related to the chromosomal type of CPM; placental dysfunction was seen predominantly in high-risk CPM pregnancies in which chromosomes 2, 3, 7, 13 or 16 were involved. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Recién Nacido Pequeño para la Edad Gestacional , Placenta , Recién Nacido , Embarazo , Femenino , Humanos , Lactante , Placenta/diagnóstico por imagen , Placenta/patología , Mosaicismo , Estudios Retrospectivos , Ultrasonografía Prenatal/métodos , Edad Gestacional , Parto , Imagen por Resonancia Magnética , Arteria Uterina/diagnóstico por imagenRESUMEN
Transpetrosal approaches are known to be associated with a significant risk of complications, including CSF leak, facial palsy, hearing impairment, venous injury, and/or temporal lobe injury. We aimed to evaluate the morbidity of the standard combined petrosal approach (CPA), defined as a combination of the posterior (retrolabyrinthine) and the anterior petrosal approach. We performed a systematic review and meta-analysis of articles reporting on clinical series of patients operated on for petroclival meningiomas through CPA. Studies that used the terminology "combined petrosal approach" without matching the aforementioned definition were excluded as well as clinical series that included less than 5 patients. A total of 8 studies were included involving 160 patients. The pooled complication rates were 3% (95% CI, 0.5-5.6) for CSF leak, 8.6% (95% CI, 4.1-13.2%) for facial palsy, 8.2% (95% CI, 3.9-12.6%) for hearing impairment, 2.8% (95% CI, 0.9-6.5%) for venous complications, and finally 4.8% (95%, 1.2-8.4%) for temporal lobe injury. Contrary to the general belief, CPA is associated with an acceptable rate of complications, especially when compared to alternative approaches to the petroclival area. In view of the major advantages like shorter trajectory, multiple angles of surgical attack, and early tumor devascularization, CPA remains an important tool in the armamentarium of the skull base surgeon.
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Parálisis Facial , Pérdida Auditiva , Neoplasias Meníngeas , Meningioma , Humanos , Parálisis Facial/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Meningioma/cirugía , Meningioma/patología , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Pérdida Auditiva/cirugía , Pérdida Auditiva/etiología , Hueso Petroso/cirugíaRESUMEN
Atom-by-atom substitution is a promising strategy for designing new cluster-based materials, which has been used to generate new gold- and silver-containing clusters. Here, the first study focused on atom-by-atom substitution of Fe and Ni to the core of a well-defined cobalt sulfide superatom [Co6 S8 L6 ]+ ligated with triethylphosphine (L = PEt3 ) to produce [Co5 MS8 L6 ]+ (M = Fe, Ni) is reported. Electrospray ionization mass spectrometry confirms the substitution of 1-6 Fe atoms with the single Fe-substituted cluster being the dominant species. The Fe-substituted clusters oxidize in solution to generate dicationic species. In contrast, only a single Ni-substituted cluster is observed, which remains stable as a singly charged species. Collision-induced dissociation experiments indicate the reduced stability of the [Co5 FeS8 L6 ]+ toward ligand loss in comparison with the unsubstituted and Ni-substituted counterparts. Density functional theory calculations provide insights into the effect of metal atom substitution on the stability and electronic structures of the clusters. The results indicate that Fe and Ni have a different impact on the electronic structure, optical, and magnetic properties, as well as ligand-core interaction of [Co6 S8 L6 ]. This study extends the atom-by-atom substitution strategy to the metal chalcogenide superatoms providing a direct path toward designing novel atomically precise core-tailored superatoms.
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BACKGROUND: The tumor immune microenvironment is a heterogeneous entity. Gene expression analysis allows us to perform comprehensive immunoprofiling and may assist in dissecting the different components of the immune infiltrate. As gene expression analysis also provides information regarding tumor cells, differences in interactions between the immune system and specific tumor characteristics can also be explored. This study aims to gain further insights in the composition of the tumor immune infiltrate and to correlate these components to histology and overall survival in non-small cell lung cancer (NSCLC). METHODS: Archival tissues from 530 early stage, resected NSCLC patients with annotated tumor and patient characteristics were analyzed using the NanoString nCounter Analysis system. RESULTS: Unsupervised clustering of the samples was mainly driven by the overall level of inflammation, which was not correlated with survival in this patient set. Adenocarcinoma (AD) showed a significantly higher degree of immune infiltration compared to squamous cell carcinoma (SCC). A 34-gene signature, which did not correlate with the overall level of immune infiltration, was identified and showed an OS benefit in SCC. Strikingly, this benefit was not observed in AD. This difference in OS in SCC specifically was confirmed in two independent NSCLC cohorts. The highest correlation between expression of the 34-gene signature and specific immune cell populations was observed for NK cells, but although a plausible mechanism for NK cell intervention in tumor growth could be established in SCC over AD, this could not be translated back to immunohistochemistry, which showed that NK cell infiltration is scarce irrespective of histology. CONCLUSIONS: These findings suggest that the ability of immune cell infiltration and the interaction between tumor and immune cells may be different between AD and SCC histology and that a subgroup of SCC tumors seems more susceptible to Natural Killer cell recognition and killing, whereas this may not occur in AD tumors. A highly sensitive technique like NanoString was able to detect this subgroup based on a 34-gene signature, but further research will be needed to assist in explaining the biological rationale of such low-level expression signatures.
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Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Humanos , Neoplasias Pulmonares/genética , Pronóstico , Microambiente TumoralRESUMEN
An orthotospovirus distinct from all other orthotospoviruses was isolated from naturally infected alstroemeria plants. Disease symptoms caused by this virus mainly consisted of yellow spots on the leaves based on which the name alstroemeria yellow spot virus (AYSV) was coined. A host range analysis was performed and a polyclonal antiserum was produced against purified AYSV ribonucleoproteins which only reacted with the homologous antigen and not with any other (established or tentative) orthotospovirus from a selection of American and Asian species. Upon thrips transmission assays the virus was successfully transmitted by a population of Thrips tabaci. The entire nucleotide sequence of the M and S RNA segments was elucidated by a conventional cloning and sequencing strategy, and contained 4797 respectively 2734 nucleotides (nt). Simultaneously, a next generation sequencing (NGS) approach (RNAseq) was employed and generated contigs covering the entire viral tripartite RNA genome. In addition to the M and S RNA nucleotide sequences, the L RNA (8865 nt) was obtained. The nucleocapsid (N) gene encoded by the S RNA of this virus consisted of 819 nucleotides with a deduced N protein of 272 amino acids and by comparative sequence alignments to other established orthotospovirus species showed highest homology (69.5% identity) to the N protein of polygonum ringspot virus. The data altogether support the proposal of AYSV as a new orthotospovirus species within a growing clade of orthotospoviruses that seem to share the Middle East basin as a region of origin.
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Alstroemeria/virología , Enfermedades de las Plantas/virología , Virus de Plantas/genética , Virus de Plantas/aislamiento & purificación , Animales , Insectos Vectores/virología , Filogenia , ARN Viral/genética , ARN Viral/aislamiento & purificación , Thysanoptera/virología , Nicotiana/virologíaRESUMEN
Objective: Young people with asthma often lack engagement in self-management. Smartphone apps offer an attractive, immediate method for obtaining asthma information and self-management support. In this research we developed an evidence-based asthma app tailored to young peoples needs, created using a participatory design approach to optimize user engagement. This paper describes the participatory design process. Methods: This multi-phased research included concept generation and ideation of app design by young people with asthma, and development of asthma information by the research team. Clinical review was sought regarding safety and accuracy of app content. Participants suggestions for improvement and any problems with the app were logged throughout. Our young co-designers were invited back to test a high fidelity prototype app using a "think aloud" process and completed a usability questionnaire. Results: Twenty asthma patients aged 15-24 years contributed to the initial app design. Three respiratory specialists and two pharmacists suggested minor corrections to clinical terminology in the app which were all incorporated. Nine co-designers acted as expert reviewers of the prototype app, of whom eight completed a usability questionnaire. Median usability scores (maximum score 6) indicated high satisfaction with app content, usefulness and ease of use [median item score 5.3 (range 4.7-6.0)]. All feedback was incorporated to create an updated prototype app. Conclusions: A clinically sound asthma app has been developed which is considered highly acceptable to the young co-designers. A six-week test of the engagement, acceptability, and usefulness of the app in young people not involved in the participatory design will follow.
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Asma/terapia , Aplicaciones Móviles , Automanejo/métodos , Diseño de Software , Adolescente , Femenino , Humanos , Masculino , Satisfacción del Paciente , Pacientes/psicología , Farmacéuticos/psicología , Proyectos de Investigación , Terapia Respiratoria/métodos , Telemedicina , Adulto JovenRESUMEN
BACKGROUND: Emergency service workers are often exposed to trauma and have increased risk of a range of mental health (MH) conditions. Smartphone applications have the potential to provide this group with effective psychological interventions; however, little is known about the acceptability and preferences regarding such initiatives. AIMS: To describe the preferences and opinions of emergency service workers regarding the use of smartphone MH applications and to examine the impact of age on these preferences. METHODS: Participants were recruited from four metropolitan Fire and Rescue NSW stations and responded to questionnaire items covering three key domains: current smartphone use, potential future use and preferences for design and content as well as therapeutic techniques. RESULTS: Overall, approximately half the sample (n = 106) claimed they would be interested in trying a tailored emergency-worker MH smartphone application. There were few differences between age groups on preferences. The majority of respondents claimed they would use an app for mental well-being daily and preferred terms such as 'well-being' and 'mental fitness' for referring to MH. Confidentiality, along with a focus on stress, sleep, exercise and resiliency were all considered key features. Behavioural therapeutic techniques were regarded most favourably, compared with other therapies. CONCLUSIONS: Emergency workers were interested in utilizing smartphone applications focused on MH, but expressed clear preferences regarding language used in promotion, features required and therapeutic techniques preferred.
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Bomberos/psicología , Salud Mental , Aplicaciones Móviles , Teléfono Inteligente/estadística & datos numéricos , Adulto , Ejercicio Físico , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Estrés Laboral , Resiliencia Psicológica , Sueño , Encuestas y CuestionariosRESUMEN
BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. PATIENTS AND METHODS: We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201). RESULTS: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. CONCLUSIONS: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.
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Biomarcadores de Tumor/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Toma de Decisiones Clínicas , Cistectomía , Femenino , Regulación Neoplásica de la Expresión Génica , Heterogeneidad Genética , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Mutación , Periodo Perioperatorio , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
OBJECTIVES: The magnetic resonance imaging (MRI) variable transverse relaxation time (T2*) depends on multiple factors, one important one being the presence of deoxyhemoglobin. We aimed to describe placental T2* measurements in normal pregnancies and in those with fetal growth restriction (FGR). METHODS: We included 24 normal pregnancies at 24-40 weeks' gestation and four FGR cases with an estimated fetal weight below the 1(st) centile. Prior to MRI, an ultrasound examination, including Doppler flow measurements, was performed. The T2* value was calculated using a gradient echo MRI sequence with readout at 16 different echo times. In normal pregnancies, repeat T2* measurements were performed and interobserver reproducibility was assessed in order to estimate the reproducibility of the method. Placental histological examination was performed in the FGR cases. RESULTS: The method was robust regarding the technical and interobserver reproducibility. However, some slice-to-slice variation existed owing to the heterogeneous nature of the normal placenta. We therefore based T2* estimations on the average of two slices from each placenta. In normal pregnancies, the placental T2* value decreased significantly with increasing gestational age, with mean ± SD values of 120 ± 17 ms at 24 weeks' gestation, 84 ± 16 ms at 32 weeks and 47 ± 17 ms at 40 weeks. Three FGR cases had abnormal Doppler flow, histological signs of maternal hypoperfusion and a reduced T2* value (Z-score < -3.5). In the fourth FGR case, Doppler flow, placental histology and T2* value (Z-score, -0.34) were normal. CONCLUSIONS: The established reference values for placental T2* may be clinically useful, as T2* values were significantly lower in FGR cases with histological signs of maternal hypoperfusion. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
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Retardo del Crecimiento Fetal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Placenta/diagnóstico por imagen , Femenino , Humanos , Embarazo , Reproducibilidad de los Resultados , Ultrasonografía Prenatal/métodosRESUMEN
BACKGROUND: The past decade has seen an increasing focus on professionalism within the medical school curriculum. This reflects the growing demand for doctors who demonstrate empathy and uphold the altruistic values of the Hippocratic Oath. Such is often challenged by the resource-constrained environments of developing nations requiring uniquely tailored interventions within these regions. PURPOSE: As part of a wider effort to develop training of medical professionalism at our institution, an initiative was pursued to assess the current knowledge about and attitudes toward medical professionalism. METHODS: The study was designed as a cross-sectional descriptive study of fourth and fifth year medical students and junior doctors. A questionnaire was adapted and revised from a previously published study. Questions were grouped into categories pertaining to knowledge about professionalism and attitudes toward professionalism. Overall, 191 questionnaires were analysed (168 students and 23 doctors). RESULTS: Junior doctors' scores were higher than medical students for all knowledge subscales but scores on the attitude subscales were significantly lower than medical students. Overall, in both groups, attitude scores were higher than knowledge scores. There was an overall trend of decreasing attitude scores as persons progressed through their training years and into clinical practice. CONCLUSIONS: Results demonstrate limited knowledge about medical professionalism but good attitudes toward this trait. Taken together, this perhaps highlights a receptivity toward more formal training within this area that is also justified by the marked decline in attitude scores over time.
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BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies-intellectual disability syndrome. One of the complications is keloid formation. Keloids are proliferative fibrous growths resulting from excessive tissue response to skin trauma. OBJECTIVES: To describe the clinical characteristics of keloids in individuals with RSTS reported in the literature and in a cohort of personally evaluated individuals with RSTS. PATIENTS AND METHODS: We performed a literature search for descriptions of RSTS individuals with keloids. All known individuals with RSTS in the Netherlands filled out three dedicated questionnaires. All individuals with (possible) keloids were personally evaluated. A further series of individuals with RSTS from the U.K. was personally evaluated. RESULTS: Reliable data were available for 62 of the 83 Dutch individuals with RSTS and showed 15 individuals with RSTS (24%) to have keloids. The 15 Dutch and 12 U.K. individuals with RSTS with keloids demonstrated that most patients have multiple keloids (n > 1: 82%; n > 5: 30%). Mean age of onset is 11·9 years. The majority of keloids are located on the shoulders and chest. The mean length × width of the largest keloid was 7·1 × 2·8 cm, and the mean thickness was 0·7 cm. All affected individuals complained of itching. Generally, treatment results were disappointing. CONCLUSIONS: Keloids occur in 24% of individuals with RSTS, either spontaneously or after a minor trauma, usually starting in early puberty. Management schedules have disappointing results. RSTS is a Mendelian disorder with a known molecular basis, and offers excellent opportunities to study the pathogenesis of keloids in general and to search for possible treatments.
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Queloide/patología , Síndrome de Rubinstein-Taybi/patología , Edad de Inicio , Estudios de Cohortes , Femenino , Humanos , Queloide/etiología , Masculino , Síndrome de Rubinstein-Taybi/etiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: In a previous study comparing the amount of visual field damage at presentation in patients having open-angle glaucoma (OAG) identified through screening and in patients diagnosed in routine clinical practice in the 1990s, the damage was considerably worse in the clinically diagnosed patients. In the present study we compare visual field damage at presentation in the same 402 screened patients with that seen in 281 newly detected previously untreated patients clinically diagnosed in the 2010s. METHODS: The perimetric visual field index mean deviation (MD) was compared in the two groups of patients. RESULTS: In the clinical patients diagnosed with bilateral visual field damage the median MD was -5.1 dB in the better eye and -13.0 dB in the worse eye. In the screened patients the median MD in the better eye was -6.5 dB and -11.5 dB in the worse eye. The differences between the clinical and screened patients were non-significant, p = 0.28 and p = 0.67 respectively. More clinical patients had severe visual field loss, defined as MD less than -20 dB, in the worse eye than in the screened patients, 18.5% versus 12.7% respectively, p = 0.037. CONCLUSION: The visual field damage at presentation in clinically diagnosed OAG patients has improved in the past 20 years, but the proportion of patients with severe visual field loss in at least one eye, almost 20%, is still unacceptably high considering that severe visual field damage at presentation is the most important risk factor for later development of glaucoma blindness.
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Glaucoma de Ángulo Abierto , Glaucoma , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/epidemiología , Suecia/epidemiología , Presión Intraocular , Glaucoma/diagnóstico , Pruebas del Campo Visual , Gravedad del Paciente , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/epidemiología , Progresión de la EnfermedadRESUMEN
C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.
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Complemento C3/análisis , Glomerulonefritis/inmunología , Glomérulos Renales/inmunología , Investigación Biomédica , Biopsia , Conducta Cooperativa , Glomerulonefritis/diagnóstico , Glomerulonefritis/terapia , Humanos , Cooperación Internacional , Glomérulos Renales/patología , Valor Predictivo de las Pruebas , PronósticoRESUMEN
OBJECTIVES: To investigate changes in human placental oxygenation during maternal hyperoxia using non-invasive blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). METHODS: Eight healthy pregnant women with uncomplicated singleton pregnancies at gestational weeks 28-36 were examined with BOLD MRI, over two consecutive 5-min periods of different oxygenation: first normoxia (21% O2 ) and then hyperoxia (12 L O2 /min), achieved by controlling the maternal oxygen supply with a non-rebreather facial mask. Selecting three slices showing cross-sections of the central part of the placenta, we investigated total placental oxygenation by drawing regions of interest (ROIs) covering the entire placenta, and regional placental oxygenation by drawing smaller ROIs in the darker and brighter areas of the placenta. For each ROI, the difference in BOLD signal between the two episodes was determined and the percentage increase in BOLD signal during hyperoxia (ΔBOLD) was calculated. RESULTS: In the BOLD image, the normoxic placenta appeared heterogeneous, with darker areas located to the fetal side and brighter areas to the maternal side. During hyperoxia, the placenta became brighter and the structure more homogeneous, and the BOLD signal of the total placenta increased (ΔBOLDtot , 15.2 ± 3.2% (mean ± SD), P < 0.0001). The increase was seen predominantly in the dark areas in the fetal part of the placenta (ΔBOLDfet , 32.1 ± 9.3%) compared with in the bright areas in the maternal part of the placenta (ΔBOLDmat , 5.4 ± 3.5%). CONCLUSION: During hyperoxia, placental oxygenation was increased predominantly in the darker placental areas, which, given their anatomical location, represent the fetal circulation of the placenta. To our knowledge, this is the first study to successfully visualize changes in placental oxygenation using BOLD MRI.
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Hiperoxia/fisiopatología , Imagen por Resonancia Magnética/métodos , Oxígeno/sangre , Placenta/fisiología , Complicaciones del Embarazo/fisiopatología , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: Cryopreservation and transplantation of the whole ovary with vascular pedicle would be helpful to prevent posttransplantation ischemia. In fact, perfusion of the intact mammalian ovary through arteries and veins is the most technically difficult part of the whole cryopreservation process because of its complexity. It is important to develop the technology of long-time perfusion of intact ovaries by cryoprotectants at low temperatures because it was established earlier that 24-hour cooling to 5 degrees C before cryopreservation is beneficial for the freezing of human ovarian tissue. The aim of this research was to study the effectiveness of perfusion of intact bovine ovaries with different rates of perfusion and elapsed time between extraction of these ovaries and beginning of perfusion. METHODS: Arteria ovarica was cannulated and ovaries were perfused with Leibovitz L-15 medium + 100 IU/mL heparin + 5% bovine calf serum + 6% dimethyl sulfoxide + 6% ethylene glycol + 0.15 M sucrose + Indian ink at room temperature (22 degrees C). In the first cycle of experiments, ovaries (n = 145) were perfused for 60 minutes during 1 to 1.5 hours after extraction of ovaries in the slaughter house at perfusion rates of 150 mL/hour (2.5 mL/minute), 100 mL/hour (1.67 mL/minute), 75 mL/hour (1.25 mL/minute), 50 mL/hour (0.83 mL/minute), 25 mL/hour (0.42 mL/minute), and 12.5 mL/hour (0.21 mL/minute) for groups 1, 2, 3, 4, 5, and 6, respectively. In the second cycle of experiments, ovaries (n = 29) were perfused with a rate of 25 mL/hour (0.42 mL/minute) for 60 minutes during the following time-periods elapsed after extraction of ovaries in the slaughter house: 3 hours (n = 18), 4 hours (n = 5), 5 hours (n = 3), and 6 hours (n = 3) for groups 1, 2, 3, and 4, respectively. Ovaries in luteal and follicular phase of development were distributed randomly into groups. Successful perfusion of blood vessels was detected visibly by a blue coloration of the vascular pedicle and ovarian tissues. The percentage of Indian ink-perfused tissues was detected. The intensity of the vascular leakage and tissue damage was scored microscopically and noted as follows: lack of disruption (-), weak disruption (+), moderate disruption (++), and strong disruption RESULTS: The first cycle of experiments shows that an optimal perfusion rate was established for groups 4 and 5 (50 and 25 mL/hour, respectively). In the second cycle of experiments, good perfusion of ovaries with the perfusion rate of 25 mL/hour was established only for ovaries of group 1 (3 hours after extraction). The effectiveness of perfusion in group 2 (4 hours after extraction) was sharply decreased. CONCLUSIONS: Effective perfusion of bovine intact ovaries with vascular pedicle with freezing medium (6% ethylene glycol + 6% dimethyl sulfoxide + 0.15 M sucrose) at room temperature includes a rate of perfusion 25 or 50 mL/ hour. Ovaries must be perfused no later than 3 hours after the death of animals.
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Criopreservación , Congelación , Ovario , Animales , Bovinos , Femenino , Técnicas In Vitro , PerfusiónRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD), due to a heterozygous mutation in PKD1 or PKD2, is usually an adult onset disease. Renal cystic disease is generally milder in PKD2 patients than in PKD1 patients. Recently, several PKD1 patients with a severe renal cystic phenotype due to a second modifying PKD1 allele, or carrying two incomplete penetrant PKD1 alleles, have been described. This study reports for the first time a patient with neonatal onset of PKD homozygous for an incomplete penetrant PKD2 missense variant due to uniparental disomy.
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Homocigoto , Mutación Missense , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Dominante/genética , Canales Catiónicos TRPP/genética , Disomía Uniparental , Secuencia de Aminoácidos , Secuencia de Bases , Análisis Mutacional de ADN , Humanos , Recién Nacido , Riñón/patología , Masculino , Datos de Secuencia Molecular , Linaje , Receptores de Superficie Celular/genética , UltrasonografíaRESUMEN
In November 2010, approximately 2% of the chrysanthemum (Chrysanthemum morifolium) cv. Paniz plants showed numerous small leaves in the top and stunting in a field collection of the National Research Center of Ornamental Plants in Mahallat, Iran. Next to these plants, some plants of the same collection showed leaves with a reddish and/or chlorotic discoloration around the veins. The observed symptoms were believed to represent infection by a phytoplasma and/or a viroid. Two plants with each type of the symptoms were individually analyzed. Using a total RNA extract from diseased leaves, RT-PCR with primer pairs targeting all known pospiviroids, including Chrysanthemum stunt viroid (CSVd) (3), were negative. Purified DNA was examined for the highly conserved phytoplasma 16S rRNA gene by nested-PCR using the universal primer sets P1/P7 and R16F2n/R16R2 (2). Fragments of 1.2 kb, obtained only from the plants with the small leaves and stunting, were sequenced and one of these sequences, which were identical, was deposited in GenBank (Accession No. KC176800). BLAST analysis of the chrysanthemum phytoplasma sequence exhibited 99% identity to Candidatus Phytoplasma phoenicium (Ca. P. phoenicium) species of the 16SrIX group. Subsequently, in silico RFLP analysis of the nested PCR product with the pDRAW32 program using AluI and TaqI restriction sites used for 16SrIX subgroups A, B, C, D, and E indicated that the 16SrIX chrysanthemum isolate belonged to subgroup D (1). Recently, based on GenBank sequences, several strains of Ca. P. phoenicium have been isolated and identified from diverse host species like Lactuca serriola, L. sativa, Solanum lycopersicon, Sonchus sp. [16SrIX-E], Carthamus tinctorius, and Prunus amygdalus [16SrIX-B] (4) in Iran. The vector species transmitting Ca. P. phoenicium to C. morifolium still needs to be identified. The leafhopper Neoaliturus fenestratus may be a potential vector as it is an often encountered efficient transmitter vector of 16SrIX group phytoplasmas in Iran (2). Next to the susceptibility of chrysanthemum to members of aster yellows, stolbur, and Ca. P. aurantifolia phytoplasma groups, this is, to our knowledge, the first report of a 16SrIX group member infecting chrysanthemum. The detection of this phytoplasma in chrysanthemum can form a new threat to this crop and other ornamentals in the Mahallat flower production region. References: (1) R. E. Davis et al. New Dis. Rep. 20:35, 2010. (2) M. Salehi et al. Plant Pathol. 56:669, 2007. (3) J. Th. J. Verhoeven et al. Eur. J. Plant Pathol. 110:823, 2004. (4) M. G. Zamharir. Afr. J. Microbiol. Res. 5:6013, 2011.
RESUMEN
BACKGROUND: Many different child weight management programmes exist, with varying degrees of evaluation to provide evidence of their success. The purpose of this research was to use a standardized approach to audit the effectiveness of weight management intervention programmes in the West Midlands region of the UK, specifically to assess the benefits to participating children in terms of health improvement and behaviour change. METHODS: An audit of seven family-based intervention programmes currently in place in the West Midlands. Programmes were audited against the Standard Evaluation Framework. RESULTS: The programmes provided a partial data set relating to a change in weight from the baseline to the end of the programme; none of the programmes provided all of the measures indicated by the Standard Evaluation Form as being essential for evaluation. Weight change ranged from an increase in group mean of 0.4 kg to a decrease of 0.9 kg. Body Mass Index SD decreased by 0.1-0.2 points in four programmes and remained unchanged in two programmes. Four programmes collected long-term follow-up data at 6 months. This was often limited because of participant dropout. Improvement in diet and exercise were reported by participants in all programmes which measured these behaviours. CONCLUSIONS: Ongoing evaluation of all programmes, using a standard approach, is essential in order to improve the evidence base and support future commissioning.
Asunto(s)
Obesidad/terapia , Programas de Reducción de Peso/normas , Adolescente , Índice de Masa Corporal , Peso Corporal , Niño , Inglaterra , Terapia Familiar , Conducta Alimentaria , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Auditoría Médica , Actividad Motora , Obesidad/fisiopatología , Evaluación de Programas y Proyectos de Salud , Resultado del Tratamiento , Circunferencia de la Cintura , Programas de Reducción de Peso/métodosRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. A gene defect located on the short arm of chromosome 16 is responsible for the disease in roughly 86% of affected European families. Using highly polymorphic microsatellite DNA markers, we have assigned a second gene for ADPKD to chromosome 4. In eight families with clear evidence against linkage to chromosome 16 markers, linkage analysis with the markers D4S231 and D4S423, demonstrated a multipoint lod score of 22.42.