RESUMEN
Autologous peripheral blood stem cell (PBSC) transplantation is crucial in pediatric cancer treatment, and tandem transplantation is beneficial in certain malignancies. Collecting PBSCs in small children with low body weight is challenging. We retrospectively analyzed data of pediatric cancer patients weighing <15 kg who underwent autologous PBSC harvesting in our hospital. Collections were performed in the pediatric intensive care unit over 2 or 3 consecutive days, to harvest sufficient stem cells (goal ≥2 × 106 CD34+ cells/kg per apheresate). From April 2006 to August 2021, we performed 129 collections after 50 mobilizations in 40 patients, with a median age of 1.9 (range, 0.6-5.6) years and a body weight of 11.0 (range, 6.6-14.7) kg. The median CD34+ cells in each apheresate were 4.2 (range, 0.01-40.13) × 106/kg. 78% and 56% of mobilizations achieved sufficient cell dose for single or tandem transplantation, respectively, without additional aliquoting. The preapheresis hematopoietic progenitor cell (HPC) count was highly correlated with the CD34+ cell yield in the apheresate (r = 0.555, P < 0.001). Granulocyte colony-stimulating factor alone was not effective for mobilization in children ≥2 years of age, even without radiation exposure. By combining the preapheresis HPC count ≥20/µL and the 3 significant host factors, including age <2 years, no radiation exposure and use of chemotherapy, the prediction rate of goal achievement was increased (area under the curve 0.787).
RESUMEN
OBJECTIVES: This study evaluated the long-term efficacy and safety of radiofrequency ablation (RFA) for intrathoracic goiter (ITG) over a follow-up period exceeding six months. METHODS: From 2017 to 2022, 22 patients (6 males, 16 females) with 24 ITGs treated with RFA at a single medical center were evaluated. All patients underwent ultrasonography (US), computed tomography (CT), or magnetic resonance imaging (MRI) before RFA. Follow-up CT/MRI was performed six months after the initial RFA and then every 6-12 months. The primary outcomes measured were the degree of extension, goiter volume, volume reduction rate (VRR), tracheal deviation, and tracheal lumen. Additionally, we assessed the outcomes of single-session RFA (n = 16) vs. multiple sessions (n = 8) on goiters and explored the correlation between ITG volume measurements obtained using ultrasonography and CT/MRI. RESULTS: The median follow-up period was 12 months (interquartile range: 6-36.8 months). At the last follow-up, the nodule volume measured by CT/MRI had significantly decreased (76.2 vs. 24.6 mL; p < 0.05), with a VRR of 64.6%. Patients who underwent multiple RFA sessions showed a significantly higher VRR than the single-session patients (63.8 vs. 80.1%, p < 0.05). The intraclass correlation between goiter volumes measured using US and CT/MRI was moderate. CONCLUSION: This study affirms the long-term efficacy and safety of RFA for ITG, providing an alternative treatment for nonsurgical candidates. Multiple RFA sessions may be beneficial for achieving better volume reduction. Sole reliance on ultrasonography is inadequate; therefore, integrating CT/MRI is essential for accurate pre-RFA and follow-up assessments.
Intrathoracic goiters significantly impact both cosmetic appearance and induce numerous compressive symptoms.Radiofrequency ablation brought notable volume reduction and persistent, effective alleviation of compressive symptoms.Radiofrequency ablation presents a promising therapeutic modality with long-term benefits for patients with intrathoracic goiter.
Asunto(s)
Imagen por Resonancia Magnética , Ablación por Radiofrecuencia , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , Femenino , Masculino , Persona de Mediana Edad , Ablación por Radiofrecuencia/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Ultrasonografía/métodos , Adulto , Resultado del Tratamiento , Bocio Subesternal/diagnóstico por imagen , Bocio Subesternal/cirugíaRESUMEN
Haploidization of the genome in meiosis requires that chromosomes be sorted exclusively into pairs stabilized by synaptonemal complexes (SCs) and crossovers. This sorting and pairing is accompanied by active chromosome positioning in meiotic prophase in which telomeres cluster near the spindle pole to form the bouquet before dispersing around the nuclear envelope. We now describe telomere-led rapid prophase movements (RPMs) that frequently exceed 1 microm/s and persist throughout meiotic prophase. Bouquet formation and RPMs depend on NDJ1, MPS3, and a new member of this pathway, CSM4, which encodes a meiosis-specific nuclear envelope protein required specifically for telomere mobility. RPMs initiate independently of recombination but differ quantitatively in mutants that fail to complete recombination, suggesting that RPMs respond to recombination status. Together with recombination defects described for ndj1, our observations suggest that RPMs and SCs balance the disruption and stabilization of recombinational interactions, respectively, to regulate crossing over.
Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Cromosomas Fúngicos/metabolismo , Meiosis , Proteínas de la Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/citología , Telómero/metabolismo , Transporte Biológico , Proteínas de Ciclo Celular/genética , Emparejamiento Cromosómico , Segregación Cromosómica , Intercambio Genético , Proteínas de la Membrana/genética , Mutación , Proteínas Nucleares , Recombinación Genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Complejo SinaptonémicoRESUMEN
Kinmen, the famous Cold War island also known as Quemoy, is a typical island with isolated power grids. It considers the promotion of renewable energy and electric charging vehicles to be two essential strategies to achieve the goal of a low-carbon island and smart grid. With this motivation in mind, the main objective of this study is to design and deploy an energy management system for hundreds of current PV sites distributed on the island, energy storage systems, and charging stations on the island. In addition, the real-time acquisition of the data for power generation, power storage, and power consumption systems will be used for future demand and response analysis. Moreover, the accumulated dataset will also be utilized for the forecast or prediction of renewable energy generated by the PV systems or power consumed by the battery units or charging stations. The results of this study are promising since a practical, robust, and workable system and database are developed and implemented with a variety of Internet of Things (IoT), data transmission technologies, and the hybrid of on-premises and cloud servers. Users of the proposed system can remotely access the visualized data through the user-friendly web-based and Line bot interfaces seamlessly.
Asunto(s)
Carbono , Suministros de Energía Eléctrica , Taiwán , Bases de Datos Factuales , InternetRESUMEN
BACKGROUND: Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan. METHODS: The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed. RESULTS: This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p < .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS. CONCLUSIONS: Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns.
Asunto(s)
Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Niño , Humanos , Adolescente , Recién Nacido , Lactante , Preescolar , Pronóstico , Cisplatino , Carboplatino/uso terapéutico , Estudios Retrospectivos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias del Mediastino/terapiaRESUMEN
The ATP binding sites of many enzymes are structurally related, which complicates their development as therapeutic targets. In this work, we explore a diverse set of ATPases and compare their ATP binding pockets using different strategies, including direct and indirect structural methods, in search of pockets attractive for drug discovery. We pursue different direct and indirect structural strategies, as well as ligandability assessments to help guide target selection. The analyses indicate human RAD51, an enzyme crucial in homologous recombination, as a promising, tractable target. Inhibition of RAD51 has shown promise in the treatment of certain cancers but more potent inhibitors are needed. Thus, we design compounds computationally against the ATP binding pocket of RAD51 with consideration of multiple criteria, including predicted specificity, drug-likeness, and toxicity. The molecules designed are evaluated experimentally using molecular and cell-based assays. Our results provide two novel hit compounds against RAD51 and illustrate a computational pipeline to design new inhibitors against ATPases.
Asunto(s)
Descubrimiento de Drogas , Recombinación Homóloga , Adenosina Trifosfatasas , Adenosina Trifosfato/química , Sitios de Unión , Humanos , Unión ProteicaRESUMEN
OBJECTIVE: The current study asked whether BQ dependence level could affect working memory (WM) and remote memory for the chewers with concurrent use of cigarettes and alcohol, a common phenomenon in Taiwan. METHODS: The standardized neuropsychological tests (Wechsler Memory Scale III (WMS-III) and Remote Memory Test) were adopted to address the BQ chewers' verbal WM, spatial WM and remote memory. The Spatial Span Test and the Digit Span Test from WMS-III and the Remote Memory Test were adopted. The Betel Nut Dependency Scale (BNDS), the Fagerstrom Test for Nicotine Dependence (FTND), and the Alcohol Use Disorders Identification Test (AUDIT) were adopted to measure the dependence levels. RESULTS: The BQ dependence level and Last BQ did not affect spatial WM, verbal WM, and remote memory. Last Cigarette is critical in affecting WM; namely, longer interval led to worse performance. Finally, higher alcohol dependence level could lead to better remote memory. CONCLUSIONS: To our knowledge, there are no BQ studies addressing the effects of concurrent use of cigarettes and alcohol on memory. The current results suggest that cigarette smoking and alcohol drinking, rather than BQ chewing, are critical for memory performance.
Asunto(s)
Alcoholismo , Productos de Tabaco , Areca , Humanos , Masticación , Memoria a Largo Plazo , Memoria a Corto Plazo , TaiwánRESUMEN
BACKGROUND: RAD51-dependent homologous recombination (HR) is one of the most important pathways for repairing DNA double-strand breaks (DSBs), and its regulation is crucial to maintain genome integrity. Elp1 gene encodes IKAP/ELP1, a core subunit of the Elongator complex, which has been implicated in translational regulation. However, how ELP1 contributes to genome maintenance is unclear. METHODS: To investigate the function of Elp1, Elp1-deficient mouse embryonic fibroblasts (MEFs) were generated. Metaphase chromosome spreading, immunofluorescence, and comet assays were used to access chromosome abnormalities and DSB formation. Functional roles of Elp1 in MEFs were evaluated by cell viability, colony forming capacity, and apoptosis assays. HR-dependent DNA repair was assessed by reporter assay, immunofluorescence, and western blot. Polysome profiling was used to evaluate translational efficiency. Differentially expressed proteins and signaling pathways were identified using a label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach. RESULTS: Here, we report that Elp1 depletion enhanced genomic instability, manifested as chromosome breakage and genotoxic stress-induced genomic DNA fragmentation upon ionizing radiation (IR) exposure. Elp1-deficient cells were hypersensitive to DNA damage and exhibited impaired cell proliferation and defective HR repair. Moreover, Elp1 depletion reduced the formation of IR-induced RAD51 foci and decreased RAD51 protein levels. Polysome profiling analysis revealed that ELP1 regulated RAD51 expression by promoting its translation in response to DNA damage. Notably, the requirement for ELP1 in DSB repair could be partially rescued in Elp1-deficient cells by reintroducing RAD51, suggesting that Elp1-mediated HR-directed repair of DSBs is RAD51-dependent. Finally, using proteome analyses, we identified several proteins involved in cancer pathways and DNA damage responses as being differentially expressed upon Elp1 depletion. CONCLUSIONS: Our study uncovered a molecular mechanism underlying Elp1-mediated regulation of HR activity and provides a novel link between translational regulation and genome stability.
Asunto(s)
Rotura Cromosómica , Daño del ADN/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Biosíntesis de Proteínas/genética , Recombinasa Rad51/genética , Reparación del ADN por Recombinación/genética , Animales , Fibroblastos , Inestabilidad Genómica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Recombinasa Rad51/metabolismoRESUMEN
We herein report the case of a girl with PRETEXT III hepatoblastoma (HB) developing recurrent lung metastases despite multiple chemotherapy regimens, aggressive tumor excision, multiple lung metastasectomies, and autologous peripheral blood stem cell transplantation. High tumor mutation burden (TMB) was identified through targeted next-generation sequencing, and pembrolizumab was administered post-operatively as a last resort. A complete and sustained response to the immune checkpoint inhibitor was achieved for 22 months. Although the majority of HB have a low TMB, immune checkpoint inhibitor therapy may be useful for patients with refractory HBs with a high TMB.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Hepatoblastoma/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundario , Preescolar , Femenino , Hepatoblastoma/patología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Trasplante de Células Madre , Resultado del TratamientoRESUMEN
In meiosis, crossovers between homologous chromosomes link them together. This enables them to attach to microtubules of the meiotic spindle as a unit, such that the homologs will be pulled away from one another at anaphase I. Homologous pairs can sometimes fail to become linked by crossovers. In some organisms, these non-exchange partners are still able to segregate properly. In several organisms, associations between the centromeres of non-exchange partners occur in meiotic prophase. These associations have been proposed to promote segregation in meiosis I. But it is unclear how centromere pairing could promote subsequent proper segregation. Here we report that meiotic centromere pairing of chromosomes in mouse spermatocytes allows the formation of an association between chromosome pairs. We find that heterochromatin regions of homologous centromeres remain associated even after centromere-pairing dissolves. Our results suggest the model that, in mouse spermatocytes, heterochromatin maintains the association of homologous centromeres in the absence crossing-over.
Asunto(s)
Centrómero , Emparejamiento Cromosómico , Segregación Cromosómica , Heterocromatina , Meiosis , Espermatocitos , Animales , Masculino , Ratones , Profase , Recombinación GenéticaRESUMEN
Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography-hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26-0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose-response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.
Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Arsénico/efectos adversos , Arsénico/orina , Desarrollo Infantil , Discapacidades del Desarrollo/inducido químicamente , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/metabolismo , Factores de Edad , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Casos y Controles , Niño , Preescolar , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/metabolismo , Discapacidades del Desarrollo/psicología , Relación Dosis-Respuesta a Droga , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Metilación , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Medición de Riesgo , Factores de Riesgo , Taiwán , Vitamina B 12/sangreRESUMEN
BACKGROUND: The incidence of immune thrombocytopenia (ITP) is not well known in Asians. The aims of this study were to survey incidences and clinical features of ITP in Taiwan. STUDY DESIGN AND METHODS: This study identified 4855 incident ITP cases from the population-based National Health Insurance Research Database from mid-2006 to mid-2013, and compared incidences, patient characteristics, and clinical manifestations of ITP by age. RESULTS: Respective ITP incidence rates among those aged <15, 15 to 59, and ≥60 years were 4.0, 2.0, and 5.4 per 100,000 person-years. A male predominance was noted in children, and a female predominance was found in adults. The most common causes of secondary ITP were systemic lupus erythematosus (21.8%), viral hepatitis C (16.9%), and viral hepatitis B (13.4%). The rate of secondary ITP in children was less than one fifth that in adults (4.2% vs. 23.8%). Rates of central nervous system (1.1%) and gastrointestinal tract bleeding (3.3%) were rare, with variations by age. The rate of splenectomies in children (0.4%) was only one tenth that in adults (4.1%). The disease in 25% of children and 30% of adults became persistent or chronic. A decreasing trend in the ITP incidence was found (annual percentage change, -4.9%), and it was confined to those aged >15 years. CONCLUSION: Incidence estimates of ITP in Taiwan were close to those of Western countries, with age-specific variations in sex ratio, comorbidity, splenectomy, secondary causes, and incidence trends. The results suggest no racial variations in ITP incidences, but a geographical difference in causes of secondary ITP.
Asunto(s)
Púrpura Trombocitopénica Idiopática/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Taiwán/epidemiología , Adulto JovenRESUMEN
During meiosis, repair of programmed DNA double-strand breaks (DSBs) by recombination promotes pairing of homologous chromosomes and their connection by crossovers. Two DNA strand-exchange proteins, Rad51 and Dmc1, are required for meiotic recombination in many organisms. Studies in budding yeast imply that Rad51 acts to regulate Dmc1's strand exchange activity, while its own exchange activity is inhibited. However, in a dmc1 mutant, elimination of inhibitory factor, Hed1, activates Rad51's strand exchange activity and results in high levels of recombination without participation of Dmc1. Here we show that Rad51-mediated meiotic recombination is not subject to regulatory processes associated with high-fidelity chromosome segregation. These include homolog bias, a process that directs strand exchange between homologs rather than sister chromatids. Furthermore, activation of Rad51 does not effectively substitute for Dmc1's chromosome pairing activity, nor does it ensure formation of the obligate crossovers required for accurate homolog segregation. We further show that Dmc1's dominance in promoting strand exchange between homologs involves repression of Rad51's strand-exchange activity. This function of Dmc1 is independent of Hed1, but requires the meiotic kinase, Mek1. Hed1 makes a relatively minor contribution to homolog bias, but nonetheless this is important for normal morphogenesis of synaptonemal complexes and efficient crossing-over especially when DSB numbers are decreased. Super-resolution microscopy shows that Dmc1 also acts to organize discrete complexes of a Mek1 partner protein, Red1, into clusters along lateral elements of synaptonemal complexes; this activity may also contribute to homolog bias. Finally, we show that when interhomolog bias is defective, recombination is buffered by two feedback processes, one that increases the fraction of events that yields crossovers, and a second that we propose involves additional DSB formation in response to defective homolog interactions. Thus, robust crossover homeostasis is conferred by integrated regulation at initiation, strand-exchange and maturation steps of meiotic recombination.
Asunto(s)
Proteínas de Ciclo Celular/genética , Intercambio Genético , Proteínas de Unión al ADN/genética , Meiosis/genética , Recombinasa Rad51/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Ciclo Celular/metabolismo , Cromátides/genética , Emparejamiento Cromosómico/genética , Segregación Cromosómica/genética , Roturas del ADN de Doble Cadena , Reparación del ADN/genética , Proteínas de Unión al ADN/metabolismo , Homeostasis , Recombinación Homóloga/genética , Recombinasa Rad51/metabolismo , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/metabolismo , Complejo Sinaptonémico/genéticaRESUMEN
The HOP2 protein is required for efficient double-strand break repair which ensures the proper synapsis of homologous chromosomes and normal meiotic progression. We previously showed that in vitro HOP2 shows two distinctive activities: when it is incorporated into a HOP2-MND1 heterodimer, it stimulates DMC1 and RAD51 recombination activities, and the purified HOP2 alone is proficient in promoting strand invasion. The structural and biochemical basis of HOP2 action in recombination are poorly understood; therefore, they are the focus of this work. Herein, we present the solution structure of the amino-terminal portion of mouse HOP2, which contains a typical winged helix DNA-binding domain. Together with NMR spectral changes in the presence of double-stranded DNA, protein docking on DNA, and mutation analysis to identify the amino acids involved in DNA coordination, our results on the three-dimensional structure of HOP2 provide key information on the fundamental structural and biochemical requirements directing the interaction of HOP2 with DNA. These results, in combination with mutational experiments showing the role of a coiled-coil structural feature involved in HOP2 self-association, allow us to explain important aspects of the function of HOP2 in recombination.
Asunto(s)
Proteínas de Ciclo Celular/química , Proteínas de Unión al ADN/química , ADN/química , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Secuencia de Aminoácidos , Aminoácidos/química , Aminoácidos/genética , Aminoácidos/metabolismo , Animales , Sitios de Unión/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , ADN/genética , ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Conformación de Ácido Nucleico , Unión Proteica , Homología de Secuencia de Aminoácido , Soluciones/químicaRESUMEN
BACKGROUND & AIMS: This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30 years after a universal hepatitis B virus immunization program was launched. METHODS: Data for hepatocellular carcinoma diagnosed in 2003-2011 were collected from the population-based Taiwan Cancer Registry. Age-standardized incidence rates were calculated to analyze and compare the changes in incidence rates and trends. More specific analyses were performed on four age groups separated by sex. RESULTS: A total of 82,856 patients were diagnosed with hepatocellular carcinoma in 2003-2011 in Taiwan, yielding an age-standardized incidence rate of 32.97 per 100,000 person-years. Hepatocellular carcinoma was predominantly diagnosed in middle-aged adults (50.1%) and elderly people (49.1%), in contrast to the low incidences in children (0.04%) and adolescents and young adults (0.8%). Striking variations in trends were found for children (annual percent change: -16.6%, 2003-2010) and adolescents and young adults (annual percent change: -7.9%, 2003-2011). The incidence rate of hepatocellular carcinoma in children decreased to zero in 2011; only a slight decline in trends occurred for the middle-aged group (annual percent change: -2%, 2003-2011), and a slight upward trend was observed for elderly people (1.3%), specifically in women (1.7%). CONCLUSIONS: In Taiwan, hepatitis B virus-related hepatocellular carcinoma was nearly eradicated in children in 2011. The findings on age-specific incidence patterns and trends of hepatocellular carcinoma suggest that different control strategies for treating this devastating disease in the future be made according to age.
Asunto(s)
Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma Hepatocelular/etiología , Niño , Preescolar , Femenino , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Incidencia , Lactante , Recién Nacido , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Sistema de Registros , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
Chromosome pairing in meiotic prophase is a prerequisite for the high fidelity of chromosome segregation that haploidizes the genome prior to gamete formation. In the budding yeast Saccharomyces cerevisiae, as in most multicellular eukaryotes, homologous pairing at the cytological level reflects the contemporaneous search for homology at the molecular level, where DNA double-strand broken ends find and interact with templates for repair on homologous chromosomes. Synapsis (synaptonemal complex formation) stabilizes pairing and supports DNA repair. The bouquet stage, where telomeres have formed a transient single cluster early in meiotic prophase, and telomere-promoted rapid meiotic prophase chromosome movements (RPMs) are prominent temporal correlates of pairing and synapsis. The bouquet has long been thought to contribute to the kinetics of pairing, but the individual roles of bouquet and RPMs are difficult to assess because of common dependencies. For example, in budding yeast RPMs and bouquet both require the broadly conserved SUN protein Mps3 as well as Ndj1 and Csm4, which link telomeres to the cytoskeleton through the intact nuclear envelope. We find that mutants in these genes provide a graded series of RPM activity: wild-type>mps3-dCC>mps3-dAR>ndj1Δ>mps3-dNTâ=âcsm4Δ. Pairing rates are directly correlated with RPM activity even though only wild-type forms a bouquet, suggesting that RPMs promote homologous pairing directly while the bouquet plays at most a minor role in Saccharomyces cerevisiae. A new collision trap assay demonstrates that RPMs generate homologous and heterologous chromosome collisions in or before the earliest stages of prophase, suggesting that RPMs contribute to pairing by stirring the nuclear contents to aid the recombination-mediated homology search.
Asunto(s)
Emparejamiento Cromosómico/genética , Meiosis , Saccharomyces cerevisiae , Telómero , Proteínas de Ciclo Celular/genética , Núcleo Celular , Centrómero/genética , Segregación Cromosómica/genética , Hibridación Fluorescente in Situ , Meiosis/genética , Proteínas de la Membrana/genética , Mutación , Proteínas Nucleares/genética , Profase/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Telómero/genéticaRESUMEN
BACKGROUND: Currently, little information is available on childhood cancer incidence rates in Eastern Asia. The objective of this study was to report the first population-based cancer surveillance of children and adolescents in Taiwan. METHODS: Data from the Taiwan Cancer Registry were examined for cancer frequencies and incidence rates among individuals ages birth to 19 years from 1995 to 2009. Types of cancers were grouped according to the International Classification of Childhood Cancer. Rates were compared by sex and age. For further comparisons with other countries, rates were age standardized to the 2000 world standard population in 5-year age groups. Trends in incidence rates also were evaluated. RESULTS: In total, 12,315 individuals were diagnosed with childhood cancers, for an age-standardized incidence rate (ASR) of 132.1 per million person-years from 1995 to 2009. The male-to-female incidence rate ratio was 1.19. Overall, leukemias were the most common cancer (ASR, 39.1 per million person-years), followed by central nervous system neoplasms (15.8 per million person-years), and lymphomas (15.3 per million person-years). During the 15-year study period, the incidence rates increased by 1% annually. Compared with other countries, the rate of hepatic tumors was 2 times greater in Taiwan. The rate of germ cell neoplasms in Taiwan was similar to that in the United States and was 1.3 to 1.9 times greater compared with Canada, Brazil, Israel, and Japan. CONCLUSIONS: Based on the current data, the observed increase in overall incidence rates was attributable only marginally to improvements in case ascertainment and diagnostic procedures. The high rates of malignant hepatic tumors and germ cell neoplasms in Taiwan suggest variations in the background risk factors.
Asunto(s)
Neoplasias/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Taiwán/epidemiología , Factores de TiempoRESUMEN
Background: Research indicates that a significant number of healthcare workers accounted for all confirmed Coronavirus disease 2019 (COVID-19) cases, and many of the infected healthcare workers were asymptomatic. During the COVID-19 outbreak, a considerable number of people in Taiwan contracted the disease. Therefore, health workers in Taiwan often experienced lack of medical resources, and this problem is worse for outer island areas. In terms of stress and mental health, this study investigated the effect of poor healthcare capacity and high workload on health workers during the COVID-19 pandemic. This study also explored mindfulness-based stress reduction and resilience in health workers. Methods: This study conducted an in-depth interview to investigate stress perceived by health workers in a hospital located on an outer island of Taiwan as well as their mental health and stress relieving strategies. Results: It was found that during the COVID-19 outbreak, some common sources of stress for health workers included exposure to infectious diseases, heavy workloads, facing ethical dilemma in clinical decision-making, and unfamiliar problems from the pandemic. These types of stress cause worries, anxiety, and depression in health workers, which affects their mental and physical health as well as their patient-care performance. Conclusion: This study proposed that mindfulness-based stress reduction and protecting mental health are important for health workers.
RESUMEN
Vitamin B12 and folic acid could reduce blood homocysteine levels, which was thought to slow down the progression of Alzheimer's disease (AD), but previous studies regarding the effect of vitamin B12 and folic acid in treatment of AD have not reached conclusive results. We searched PubMed and Embase until January 12, 2023. Only randomized control trials involving participants clearly diagnosed with AD and who received vitamin B12 and folic acid were enrolled. Five studies that met the criteria were selected for inclusion in the meta-analysis. Changes in cognitive function were measured based on either the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Changes in daily life function and the level of blood homocysteine were also investigated. After a 6-month treatment, administration of vitamin B12 and folic acid improved the MMSE scores more than placebo did (SMD = 0.21, 95% CI = 0.01 to 0.32, p = 0.04) but did not significantly affect ADAS-Cog scores (SMD = 0.06, 95% CI = -0.22 to 0.33, p = 0.68) or measures of daily life function. Blood homocysteine levels were significantly decreased after vitamin B12 and folic acid treatment. Participants with AD who received 6 months of vitamin B12 and folic acid supplementation had better MMSE scores but had no difference in ADAS-Cog scores. Daily life function did not improve after treatment.
Asunto(s)
Enfermedad de Alzheimer , Ácido Fólico , Homocisteína , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina B 12 , Humanos , Ácido Fólico/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/sangre , Vitamina B 12/uso terapéutico , Vitamina B 12/sangre , Homocisteína/sangre , Cognición/efectos de los fármacosRESUMEN
Telomere-led rapid chromosome movements (RPMs) are a conserved characteristic of chromosome dynamics in meiosis. RPMs have been suggested to influence critical meiotic functions such as DNA repair and the association of the homologous chromosomes. Here, we describe a method using 3D time-lapse fluorescence imaging to monitor RPMs in Hoechst-stained mouse seminiferous tubules explants. We supplement visualization with customized quantitative motion analysis and in silico simulation. The ability to carry out live imaging, combined with quantitative image analysis, offers a sensitive tool to investigate the regulation of RPMs, chromosome reorganizations that precede dynamic mid-prophase events, and their contribution to faithful transmission of genetic information.