RESUMEN
PURPOSE: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families. METHODS: Including 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10,000 person-years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the study design, we primarily focused on cancer risk in women. RESULTS: We found significant increased risks of colorectal cancer (CRC; SIR = 1.43, 95% CI = 1.14-1.76; AER = 1.43) and hematological cancers (SIR = 1.32; 95% CI = 1.02-1.67; AER = 0.87). CRC was significantly more frequent from age 45 onward. CONCLUSION: A significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well; however, further research is needed to determine who may profit from this additional colorectal surveillance.
Asunto(s)
Neoplasias de la Mama , Quinasa de Punto de Control 2 , Neoplasias Colorrectales , Humanos , Quinasa de Punto de Control 2/genética , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Adulto , Masculino , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/epidemiología , Predisposición Genética a la Enfermedad , Anciano , Factores de Riesgo , Países Bajos/epidemiología , Proteínas Serina-Treonina Quinasas/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/epidemiología , Linaje , Incidencia , Adolescente , Adulto JovenRESUMEN
BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. METHODOLOGY: ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). RESULTS: In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. CONCLUSIONS: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.
Asunto(s)
COVID-19 , Sinusitis , Enzima Convertidora de Angiotensina 2 , Humanos , Peptidil-Dipeptidasa A , SARS-CoV-2RESUMEN
AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Euphorbiaceae/química , Flavonoides/farmacología , Odontoblastos/efectos de los fármacos , Células Madre/efectos de los fármacos , Células Cultivadas , Pulpa Dental/citología , Humanos , Proteínas Quinasas Activadas por Mitógenos , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Raíz del Diente , Microtomografía por Rayos XRESUMEN
AIM: Despite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). METHODS: Using the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. RESULTS: Adjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09-1.73], 1.33 (95% CI: 1.06-1.68) and 1.35 (95% CI: 1.07-1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan-Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. CONCLUSION: Increased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.
Asunto(s)
Glucemia , Ayuno , Enfermedad de Parkinson , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Ayuno/sangre , Humanos , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Factores de RiesgoRESUMEN
The aim of this study is to examine the clinical characteristics of children suspected to have neurodevelopmental disorders and to present features that could be helpful diagnostic clues at the clinical assessment stage. All children who visited the interdisciplinary clinic for developmental problems from May 2001 to December 2014 were eligible for this study. Medical records of the children were reviewed. A total of 1,877 children were enrolled in this study. Most children were classified into four major diagnostic groups: global developmental delay (GDD), autism spectrum disorder (ASD), developmental language disorder (DLD) and motor delay (MD). GDD was the most common (43.9%), and boys were significantly more predominant than girls in all groups. When evaluating the predictive power of numerous risk factors, the probability of GDD was lower than the probability of ASD among boys, while the probability of GDD increased as independent walking age increased. Compared with GDD and DLD, the probability of GDD was increased when there was neonatal history or when the independent walking age was late. Comparison of ASD and DLD showed that the probability of ASD decreased when a maternal history was present, whereas the probability of ASD increased with male gender. To conclude, the present study revealed the clinical features of children with various neurodevelopmental disorders. These results are expected to be helpful for more effectively flagging children with potential neurodevelopmental disorders in the clinical setting.
Asunto(s)
Trastornos del Neurodesarrollo/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Actividad Motora , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/psicología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
In vitro (or cell-free) reconstitution is a powerful tool to study the physical basis of cytoskeletal organization in eukaryotic cells. Cytoskeletal reconstitution studies have mostly been done for individual cytoskeleton systems in unconfined 3D or quasi-2D geometries, which lack complexity relative to a cellular environment. To increase the level of complexity, we present a method to study co-organization of two cytoskeletal components, namely microtubules and actin filaments, confined in cell-sized water-in-oil emulsion droplets. We show that centrosome-nucleated dynamic microtubules can be made to interact with actin filaments through a tip-tracking complex consisting of microtubule end-binding proteins and an actin-microtubule cytolinker. In addition to the protocols themselves, we discuss the optimization steps required in order to build these more complex in vitro model systems of cytoskeletal interactions.
Asunto(s)
Citoesqueleto de Actina/metabolismo , Emulsiones , Microtúbulos/metabolismo , Citoesqueleto de Actina/química , Actinas/metabolismo , Centrosoma/metabolismo , Citoesqueleto/metabolismo , Interpretación Estadística de Datos , Gotas Lipídicas/ultraestructura , Lípidos/química , Técnicas Analíticas Microfluídicas , Microfluídica/instrumentación , Microfluídica/métodos , Microtúbulos/química , Unión ProteicaRESUMEN
Cell polarity - the morphological and functional differentiation of cellular compartments in a directional manner - is required for processes such as orientation of cell division, directed cellular growth and motility. How the interplay of components within the complexity of a cell leads to cell polarity is still heavily debated. In this Review, we focus on one specific aspect of cell polarity: the non-uniform accumulation of proteins on the cell membrane. In cells, this is achieved through reaction-diffusion and/or cytoskeleton-based mechanisms. In reaction-diffusion systems, components are transformed into each other by chemical reactions and are moving through space by diffusion. In cytoskeleton-based processes, cellular components (i.e. proteins) are actively transported by microtubules (MTs) and actin filaments to specific locations in the cell. We examine how minimal systems - in vitro reconstitutions of a particular cellular function with a minimal number of components - are designed, how they contribute to our understanding of cell polarity (i.e. protein accumulation), and how they complement in vivo investigations. We start by discussing the Min protein system from Escherichia coli, which represents a reaction-diffusion system with a well-established minimal system. This is followed by a discussion of MT-based directed transport for cell polarity markers as an example of a cytoskeleton-based mechanism. To conclude, we discuss, as an example, the interplay of reaction-diffusion and cytoskeleton-based mechanisms during polarity establishment in budding yeast.
Asunto(s)
Citoesqueleto de Actina/metabolismo , Membrana Celular/metabolismo , Polaridad Celular , Escherichia coli/metabolismo , Microtúbulos/metabolismo , Saccharomyces cerevisiae/metabolismo , Citoesqueleto de Actina/ultraestructura , Adenosina Trifosfatasas/metabolismo , Proteínas Bacterianas/metabolismo , Transporte Biológico , Proteínas de Ciclo Celular/metabolismo , División Celular , Membrana Celular/ultraestructura , Proteínas del Citoesqueleto/metabolismo , Difusión , Escherichia coli/ultraestructura , Proteínas de Escherichia coli/metabolismo , Microtúbulos/ultraestructura , Modelos Biológicos , Saccharomyces cerevisiae/ultraestructura , Termodinámica , Proteína de Unión al GTP cdc42/metabolismoRESUMEN
OBJECTIVE: To learn how to configure a patient communication aid (PCA) to facilitate shared decision-making (SDM) about treatment for advanced cancer. METHODS: The PCA consists of education about SDM, a question prompt list, and values clarification methods. Study 1. A first version was presented to 13 patients, 8 relatives and 14 bereaved relatives in interviews. Study 2. A second version was used by 18 patients in a pilot study. Patients and oncologists were interviewed, patients were surveyed, and consultations were audio-recorded. RESULTS: Respondents reported that the aid facilitated patient control over information, raised choice awareness and promoted elaboration. Risks were identified, most importantly that the aid might upset patients. Also, some respondents reported that the PCA did not, or would not support decision making because they felt sufficiently competent, did not perceive a role for themselves, or did not perceive that the decision required elaboration. CONCLUSIONS: Opinions on the usefulness of the PCA varied. It was challenging to raise awareness about the presence of a choice, and to find a balance between comprehensive information and sensitivity. PRACTICE IMPLICATIONS: A future study should demonstrate whether the PCA can improve SDM, and whether this effect is stronger when oncologists receive training.
Asunto(s)
Toma de Decisiones , Neoplasias/terapia , Educación del Paciente como Asunto , Participación del Paciente , Relaciones Médico-Paciente , Adulto , Comunicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Neoplasias/psicología , Cuidados Paliativos/psicología , Proyectos Piloto , Evaluación de Programas y Proyectos de SaludRESUMEN
BACKGROUND: Sevoflurane and desflurane are widely used in balanced anaesthesia in combination with opioid analgesics. The opioid remifentanil is frequently chosen because of its extremely rapid pharmacokinetics. However, intraoperative high-dose remifentanil is associated with increased postoperative pain and rescue analgesic use owing to acute tolerance and opioid-induced hyperalgesia. This study aimed to compare intraoperative remifentanil requirements during equi-minimum alveolar concentration (MAC) sevoflurane and desflurane anaesthesia via surgical pleth index-guided remifentanil administration. METHODS: Eighty-two subjects undergoing laparoscopic cholecystectomy were randomly allocated to two groups receiving either sevoflurane (n=40) or desflurane (n=42). Anaesthesia was maintained with the assigned inhaled anaesthetics and remifentanil. End-tidal anaesthetic concentration was maintained at age-corrected 1.0 MAC, and remifentanil infusion was continuously adjusted to achieve a surgical pleth index of 20-50. Mean remifentanil infusion rate, which was the primary outcome of the study, was calculated as the total infused remifentanil dose per kg body weight per minute of total operative time. RESULTS: Mean remifentanil infusion rate [mean (standard deviation)] was significantly higher in the sevoflurane group than in the desflurane group [0.192 (0.064) vs. 0.099 (0.033) µg kg-1 min-1; difference, 0.093 (95% confidence interval, 0.071-0.115); P<0.001]. CONCLUSIONS: During equi-MAC anaesthesia of 1.0 MAC, sevoflurane and desflurane did not show similar intraoperative remifentanil consumption under surgical pleth index-guided opioid administration. Further studies using other monitors with different measuring mechanisms are warranted to determine the cause of this difference. CLINICAL TRIAL REGISTRATION: NCT02830243 (ClinicalTrials.gov).
Asunto(s)
Analgesia/métodos , Anestésicos por Inhalación , Anestésicos Intravenosos , Desflurano , Remifentanilo , Sevoflurano , Adulto , Anciano , Algoritmos , Colecistectomía Laparoscópica/métodos , Monitores de Conciencia , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
We evaluated the effect of pre-operative serratus anterior plane block on postoperative pain and opioid consumption after thoracoscopic surgery. We randomly allocated 89 participants to block with 30 ml ropivacaine 0.375% (n = 44), or no block without placebo or sham procedure (n = 45). We analysed results from 42 participants in each group. Serratus anterior plane block reduced mean (SD) remifentanil dose during surgery, 0.12 (0.06) mg.h-1 vs. 0.16 (0.06) mg.h-1 , p = 0.016, and reduced mean (SD) fentanyl consumption in the first 24 postoperative hours, 3.8 (1.9) µg.kg-1 vs. 5.7 (1.6) µg.kg-1 , p = 0.000004. Block also reduced the worst median (IQR [range]) pain scores reported in the first 24 postoperative hours: 6 (5-7 [3-10]) vs. 7 (6-7 [3-10]), p = 0.027. Block decreased dissatisfaction with pain management, categorised as 'highly unsatisfactory', 'unsatisfactory', 'neutral', 'satisfactory' or 'highly satisfactory': 1/2/21/18/0 vs. 1/14/15/11/1, p = 0.0038. There were no differences in the rates of nausea, vomiting, dizziness or length of hospital stay. Serratus anterior plane block may be used to reduce pain and opioid use after thoracoscopic lung surgery.
Asunto(s)
Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Toracoscopía/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/administración & dosificación , Esquema de Medicación , Femenino , Fentanilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Dolor Postoperatorio/etiología , Satisfacción del Paciente , Remifentanilo/administración & dosificación , Adulto JovenRESUMEN
AIM: To investigate whether magnetic resonance imaging (MRI) can improve the positive predictive value (PPV) for Breast Imaging-Reporting and Data System (BI-RADS) category 4B mammographic microcalcification. MATERIALS AND METHODS: One hundred and eight consecutive patients with BI-RADS category 4B microcalcification without mass on mammography underwent breast MRI and subsequent histopathological confirmation between January 2009 and December 2015. Mammography and MRI findings were reviewed retrospectively, and imaging features were analysed according to the 5th edition of BI-RADS. The PPV of each descriptor was analysed to identify subgroups in which PPV could be improved by the addition of MRI. RESULTS: When the criteria of presence of enhancement on MRI was applied to category 4B microcalcification, PPV increased from 0.38 (41 of 108) to 0.82 (37 of 45) and reduced benign biopsy results by 88% (59 of 67). Four ductal carcinoma in situ lesions were missed. For amorphous microcalcification with regional or grouped distribution, MRI images increased PPV without missing malignancy. CONCLUSION: Breast MRI has the potential to improve PPV for category 4B mammographic microcalcification by reducing false-positive findings. If amorphous microcalcification with regional or grouped distribution on mammography shows no enhancement on MRI, follow-up could be considered rather than immediate biopsy. In addition, breast MRI might have the potential to guide the best site to biopsy in category 4B microcalcification.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Biopsia , Errores Diagnósticos/estadística & datos numéricos , Reacciones Falso Positivas , Femenino , Humanos , Mamografía , Persona de Mediana Edad , Valor Predictivo de las Pruebas , República de Corea , Estudios RetrospectivosRESUMEN
AIM: To investigate whether pretreatment magnetic resonance imaging (MRI) features are associated with diagnostic accuracy of post-treatment MRI for predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with breast cancer. MATERIALS AND METHODS: From January 2005 and December 2016, 221 consecutive patients (mean age, 50 years; range, 20-81 years) who had undergone NAC, breast MRI before and after NAC, and surgery for invasive breast cancer were enrolled. Pretreatment and post-treatment MRI images were reviewed. Radiological complete response (rCR) was defined as the absence of both early and late enhancement on MRI after NAC. The association of pretreatment MRI features and post-treatment MRI diagnostic accuracy was assessed by using logistic regression analysis. RESULTS: Among 221 patients, 60 (27.1%) underwent pCR after NAC. The diagnostic accuracy of post-treatment MRI was 84.2% (186/221). False-positive diagnosis occurred in 21 cases and false-negative diagnosis occurred in 14 cases. Of pretreatment features, the presence of peritumoural oedema (odds ratio, 3; 95% confidence interval [CI]: 1.1, 8.0; p=0.03) and HER2 (human epidermal growth factor receptor 2)-positive status (odds ratio, 3.4; 95% CI: 1.2, 9.9; p=0.02) were significantly associated with false-positive MRI results. Dense fibroglandular tissue (odds ratio, 10.8; 95% CI: 1.1, 105.2; p=0.04), presence of rim enhancement (odds ratio, 7.5; 95% CI: 1.2, 38.3; p=0.02) and oestrogen receptor (ER)-positive status (odds ratio, 6.3; 95% CI: 1.2, 32.5; p=0.03) were significantly associated with false-negative MRI results. CONCLUSION: Pretreatment MRI features and cancer subtypes may be associated with diagnostic accuracy of post-treatment MRI after NAC in patients with breast cancer.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Adulto , Anciano , Anciano de 80 o más Años , Mama/diagnóstico por imagen , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Wogonin, a flavonoid isolated from Scutellaria baicalensis, has attracted increasing scientific attention in recent years because of its potent anti-tumor activity. Its role during viral infection has largely been unexplored. Wogonin treatment effectively suppressed both influenza A and B virus replication in Madin-Darby Canine Kidney (MDCK) cells and human lung epithelial (A549) cells. In contrast, wogonin treatment following influenza A virus infection led to up-regulation of interferon (IFN)-induced antiviral signaling. Additionally, influenza A virus infection in A549 cells induced 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and activation in a time-dependent manner and wogonin treatment led to the suppression of AMPK phosphorylation. Furthermore, the treatment with AMPK-specific inhibitor (compound C; CC) attenuated influenza A virus replication. These data suggest that wogonin possesses a potent anti-influenza activity mediated by regulation of AMPK activation, suggesting that wogonin has the potential to be developed as an anti-influenza drug.
Asunto(s)
Antivirales/farmacología , Flavanonas/farmacología , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Scutellaria baicalensis/química , Adenilato Quinasa/antagonistas & inhibidores , Adenilato Quinasa/metabolismo , Animales , Antivirales/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Perros , Flavanonas/química , Humanos , Estructura Molecular , Ensayo de Placa ViralRESUMEN
Fungal endophytes comprise one of the most ubiquitous groups of plant symbionts. They live asymptomatically within vascular plants, bryophytes and also in close association with algal photobionts inside lichen thalli. While endophytic diversity in land plants has been well studied, their diversity in lichens and bryophytes are poorly understood. Here, we compare the endolichenic and endophytic fungal communities isolated from lichens and bryophytes in the Barton Peninsula, King George Island, Antarctica. A total of 93 fungal isolates were collected from lichens and bryophytes. In order to determine their identities and evolutionary relationships, DNA sequences of the nuclear internal transcribed spacer (ITS), nuclear ribosomal small subunit (nuSSU), nuclear large subunit (nuLSU), and mitochondrial SSU (mtSSU) rDNA were obtained and protein coding markers of the two largest subunit of RNA polymerase II (RPB1 and RPB2) were generated. Multilocus phylogenetic analyses revealed that most of the fungal isolates were distributed in the following six classes in the phylum Ascomycota: Dothideomycetes, Eurotiomycetes, Lecanoromycetes, Leotiomycetes, Pezizomycetes and Sordariomycetes. For the first time we report the presence of subphylum Mortierellomycotina that may belong to an undescribed order in endophytic fungi. Taken together, our results imply that lichens and bryophytes provide similar niches and harbour a selection of these fungi, indicating generalists within the framework of evolutionary adaptation.
RESUMEN
OBJECTIVE: To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). METHODS: Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). RESULTS: Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. CONCLUSIONS: IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. SIGNIFICANCE: These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development.
Asunto(s)
Isquemia Encefálica/diagnóstico , Ondas Encefálicas , Epilepsia/diagnóstico , Hemorragia Subaracnoidea/complicaciones , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Epilepsia/epidemiología , Humanos , Periodicidad , Hemorragia Subaracnoidea/diagnósticoRESUMEN
OBJECTIVE: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have gained popularity as a promising cell source for regenerative medicine, but limited in vivo studies have reported cartilage repair. In addition, the roles of MSCs in cartilage repair are not well-understood. The purpose of this study was to investigate the feasibility of transplanting hUCB-MSCs and hyaluronic acid (HA) hydrogel composite to repair articular cartilage defects in a rabbit model and determine whether the transplanted cells persisted or disappeared from the defect site. DESIGN: Osteochondral defects were created in the trochlear grooves of the knees. The hUCB-MSCs and HA composite was transplanted into the defect of experimental knees. Control knees were transplanted by HA or left untreated. Animals were sacrificed at 8 and 16 weeks post-transplantation and additionally at 2 and 4 weeks to evaluate the fate of transplanted cells. The repair tissues were evaluated by gross, histological and immunohistochemical analysis. RESULTS: Transplanting hUCB-MSCs and HA composite resulted in overall superior cartilage repair tissue with better quality than HA alone or no treatment. Cellular architecture and collagen arrangement at 16 weeks were similar to those of surrounding normal articular cartilage tissue. Histological scores also revealed that cartilage repair in experimental knees was better than that in control knees. Immunohistochemical analysis with anti-human nuclear antibody confirmed that the transplanted MSCs disappeared gradually over time. CONCLUSION: Transplanting hUCB-MSCs and HA composite promote cartilage repair and interactions between hUCB-MSCs and host cells initiated by paracrine action may play an important role in cartilage repair.
Asunto(s)
Cartílago Articular/lesiones , Condrogénesis , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Ácido Hialurónico/uso terapéutico , Hidrogel de Polietilenoglicol-Dimetacrilato/uso terapéutico , Traumatismos de la Rodilla/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Cartílago Articular/patología , Rastreo Celular , Colágeno/metabolismo , Humanos , Traumatismos de la Rodilla/patología , Masculino , Conejos , Medicina RegenerativaRESUMEN
Atrial fibrillation is the most frequent arrhythmia after thoracic surgery and is associated with increased hospital costs, morbidity and mortality. In this study, we aimed to identify potentially modifiable risk factors for postoperative atrial fibrillation following lung resection surgery and to suggest possible measures to reduce risk. We retrospectively reviewed the medical records of 4731 patients who underwent lobectomy or more major lung resection over a 6-year period. Patients who developed atrial fibrillation postoperatively and required treatment were included in the postoperative atrial fibrillation group, while the remaining patients were assigned to the non-postoperative atrial fibrillation group. Risk factors for postoperative atrial fibrillation were analysed by multivariate analysis and propensity score matching. Overall, 12% of patients developed postoperative atrial fibrillation. Potentially modifiable risk factors for postoperative atrial fibrillation were excessive alcohol consumption (odds ratio (OR) = 1.48, 95% CI 1.08-2.02, p = 0.0140), red cell transfusion (2.70(2.13-3.43), p < 0.0001), use of inotropes (1.81(1.42-2.31), p < 0.0001) and open (vs. thoracoscopic) surgery (1.59(1.23-2.05), p < 0.0001). Compared with inotrope use, vasopressor administration was not related to postoperative atrial fibrillation. Use of steroids or thoracic epidural anaesthesia did not reduce the incidence of postoperative atrial fibrillation. We conclude that high alcohol consumption, red cell transfusion, use of inotropes and open surgery are potentially modifiable risk factors for postoperative atrial fibrillation. Pre-operative alcohol consumption needs to be addressed. Avoiding red cell transfusion and performing lung resection via video-assisted thoracoscopic surgery may reduce the incidence of postoperative atrial fibrillation and the administration of vasopressors rather than inotropes is preferred.
Asunto(s)
Fibrilación Atrial/etiología , Neumonectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Transfusión de Eritrocitos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: Mesenchymal-epithelial interactions are important in controlling hair growth and the hair cycle. The ß-catenin pathway of dermal papilla cells (DPCs) plays a pivotal role in morphogenesis and normal regeneration of hair follicles. Deletion of ß-catenin in the dermal papilla reduces proliferation of the hair follicle progenitor cells that generate the hair shaft and induces an early onset of the catagen phase. In this study, a modulator of the Wnt/ß-catenin activity was studied in oriental herb extracts on cultured human DPCs. METHODS: The effect of Malva verticillata (M. verticillata) seeds on human DPCs was investigated by a Wnt/ß-catenin reporter activity assay system (ß-catenin-TCF/LEF reporter gene) and cell proliferation analysis. The synthesis of the factors related to hair growth and cycling was measured at both the mRNA and the protein level by semi-quantitative PCR and Western blot analysis, respectively. RESULTS: An extract from M. verticillata seeds increased Wnt reporter activity in a concentration-dependent manner and also led to increased ß-catenin levels in cultured human DPCs. Myristoleic acid, identified as an effective compound of M. verticillata seeds, stimulated the proliferation of DPCs in a dose-dependent manner and increased transcription levels of the downstream targets: IGF-1, KGF, VEGF and HGF. Myristoleic acid also enhanced the phosphorylation of MAPKs (Akt and p38). CONCLUSION: Overall, the data suggest that this extract of M. verticillata seeds could be a good candidate for treating hair loss by modulating the Wnt/ß-catenin pathway in DPCs.