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BACKGROUND: Acute cholecystitis (AC) is a common surgical emergency. The Tokyo Guidelines 2018 (TG18) provides a reliable algorithm for the treatment of AC patients to achieve optimal outcomes. However, the economic benefits have not been validated. We hypothesize that good outcomes and cost savings can both be achieved if patients are treated according to the TG18. METHOD: This retrospective study included 275 patients who underwent cholecystectomy in a 15-month span. Patients were divided into three groups (group 1: mild AC; group 2: moderate AC with American Society of Anesthesiologists (ASA) physical status class ≤ 2 and Charlson Comorbidity Index (CCI) score ≤ 5; and group 3: moderate AC with ASA class ≥ 3, CCI score ≥ 6, or severe AC). Each group was further divided into two subgroups according to management (followed or deviated from the TG18). Patient demographics, clinical outcomes, and hospital costs were compared. RESULTS: For group 1 patients, 77 (81%) were treated according to the TG18 and had a significantly higher successful laparoscopic cholecystectomy (LC) rate (100%), lower hospital cost ($1896 vs $2388), and shorter hospital stay (2.9 vs 8 days) than those whose treatment deviated from the TG18. For group 2 patients, 50 (67%) were treated according to the TG18 and had a significantly lower hospital cost ($1926 vs $2856), shorter hospital stay (3.9 vs 9.9 days), and lower complication rate (0% vs 12.5%). For group 3 patients, 62 (58%) were treated according to the TG18 and had a significantly lower intensive care unit (ICU) admission rate (9.7% vs 25%), but a longer hospital stay (12.6 vs 7.8 days). However, their hospital costs were similar. Early LC in group 3 patients did not have economic benefits over gallbladder drainage and delayed LC. CONCLUSION: The TG18 are the state-of-the-art guidelines for the treatment of AC, achieving both satisfactory outcomes and cost-effectiveness.
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Colecistectomia Laparoscópica , Colecistite Aguda , Colecistite Aguda/cirurgia , Gastos em Saúde , Humanos , Tempo de Internação , Estudos Retrospectivos , Tóquio , Resultado do TratamentoRESUMO
Containing an ensemble of nitrogen-vacancy centers in crystal matrices, fluorescent nanodiamonds (FNDs) are a new type of photostable markers that have found wide applications in light microscopy. The nanomaterial also has a dense carbon core, making it visible to electron microscopy. Here, we show that FNDs encapsulated in biotinylated lipids (bLs) are useful for subdiffraction imaging of antigens on cell surface with correlative light-electron microscopy (CLEM). The lipid encapsulation enables not only good dispersion of the particles in biological buffers but also high specific labeling of live cells. By employing the bL-encapsulated FNDs to target CD44 on HeLa cell surface through biotin-mediated immunostaining, we obtained the spatial distribution of these antigens by CLEM with a localization accuracy of â¼50 nm in routine operations. A comparative study with dual-color imaging, in which CD44 was labeled with FND and MICA/MICB was labeled with Alexa Fluor 488, demonstrated the superior performance of FNDs as fluorescent fiducial markers for CLEM of cell surface antigens.
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Antígenos de Superfície/química , Corantes Fluorescentes/química , Luz , Nanoestruturas/química , Células HeLa , Humanos , Microscopia Eletrônica , Estrutura Molecular , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice for gallbladder lesions, but it is not a pain-free procedure. This study explored the pain relief provided by combined wound and intraperitoneal local anesthetic use for patients who are undergoing LC. METHODS: Two-hundred and twenty consecutive patients undergoing LC were categorized into 1 of the following 4 groups: local wound anesthetic after LC either with an intraperitoneal local anesthetic (W + P) (group 1) or without an intraperitoneal local anesthetic (W + NP) (group 2), or no local wound anesthetic after LC either with intraperitoneal local anesthetic (NW + P) (group 3) or without an intraperitoneal local anesthetic (NW + NP) (group 4). A visual analog scale (VAS) was used to assess postoperative pain. The amount of analgesic used and the duration of hospital stay were also recorded. RESULTS: The VAS was significantly lower immediately after LC for the W + P group than for the NW + NP group (5 vs. 6; p = 0.012). Patients in the W + P group received a lower total amount of meperidine during their hospital stay. They also had the shortest hospital stay after LC, compared to the patients in the other groups. CONCLUSION: Combined wound and intraperitoneal local anesthetic use after LC significantly decreased the immediate postoperative pain and may explain the reduced use of meperidine and earlier discharge of patients so treated.
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Amidas/administração & dosagem , Anestesia Local/métodos , Anestésicos Locais/administração & dosagem , Colecistectomia Laparoscópica , Dor Pós-Operatória/prevenção & controle , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas/uso terapêutico , Anestésicos Locais/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Ropivacaina , Resultado do TratamentoRESUMO
Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.
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Background: The use of nanodiamonds (NDs) and fluorescent nanodiamonds (FNDs) as nonallergenic biocompatible additives in incomplete Freund's adjuvant (IFA) to elicit immune responses in vivo was investigated. Methods: C57BL/6 mice were immunized with chicken egg ovalbumin (OVA) in IFA and also OVA-conjugated NDs (or OVA-conjugated FNDs) in IFA to produce antibodies. OVA-expressing E.G7 lymphoma cells and OVA-negative EL4 cells were inoculated in mice to induce tumor formation. Results: The new formulation significantly enhanced immune responses and thus disease resistance. It exhibited specific therapeutic activities, effectively inhibiting the growth of E.G7 tumor cells in mice over 35 days. Conclusion: The high biocompatibility and multiple functionalities of NDs/FNDs render them applicable as active and trackable vaccine adjuvants and antitumor agents.
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Nanodiamantes , Animais , Camundongos , Camundongos Endogâmicos C57BL , Emulsões , Ovalbumina , Corantes , VacinaçãoRESUMO
BACKGROUND AND OBJECTIVES: Gastric adenocarcinoma (GC) occurs frequently in the sixth decade of life and is uncommon in patients aged 40 years or younger. The aims of this study were to define the clinicopathological features and elucidate the prognostic factors of GC in the young. METHODS: Between 1998 and 2006, 1,815 GC patients undergoing resection were enrolled in a prospective database. The findings for 115(6.0%) patients aged 40 years or younger were compared with those of 1,009 patients between 56 and 75 years old. RESULTS: The group of young patients with GC included significantly more women than the group of old patients (60.0% vs. 37.0%, respectively); young patients also had more T4 lesions (73.9% vs. 61.6%), undifferentiated tumors (85.2% vs. 55.1%), severe desmoplasia (41.4%vs. 12.2%), Lauren's diffuse-type cancers (55.6% vs. 27.7%), and perineural invasion (69.1% vs. 46.1%). Survival rates in younger patients at 3, 5, and 10 years after resection were 56.8%, 52.0%, and 42.1%, respectively, similar to those in older patients (P » 0.411). Unfavorable independent prognostic factors of GC in the young were degree of nodal involvement (N3 vs. N0; P » 0.001), advanced T status (T34 vs.T12; P » 0.015), tumor size (>4 vs. ≤4 cm; P » 0.019), and status of resection margins (positive vs. negative; P » 0.044). CONCLUSIONS: GC tends to exhibit more aggressive tumor behavior in young patients than in old patients; however, the surgical survival of young and old patients was similar. Advanced nodal involvement (N3) is the most important independent prognostic factor in the young.
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Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Feminino , Gastrectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Distribuição por Sexo , Neoplasias Gástricas/terapiaRESUMO
BACKGROUND: For patients sustaining major trauma, preinjury warfarin use may make adequate haemostasis difficult. This study aimed to determine whether preinjury warfarin would result in more haemostatic interventions (transarterial embolization [TAE] or surgeries) and a higher failure rate of nonoperative management for blunt hepatic, splenic or renal injuries. METHODS: This was a retrospective cohort study from the Taiwan National Health Insurance Research Database (NHIRD) from 2003 to 2015. Patients with hepatic, splenic or renal injuries were identified. The primary outcome measurement was the need for invasive procedures to stop bleeding. One-to-two propensity score matching (PSM) was used to minimize selection bias. RESULTS: A total of 37,837 patients were enrolled in the study, and 156 (0.41%) had preinjury warfarin use. With proper 1:2 PSM, patients who received warfarin preinjury were found to require more haemostatic interventions (39.9% vs. 29.1%, p=0.016). The differences between the two study groups were that patients with preinjury warfarin required more TAE than the controls (16.3% vs 8.2%, p = 0.009). No significant increases were found in the need for surgeries (exploratory laparotomy (5.2% vs 3.6%, p = 0.380), hepatorrhaphy (9.2% vs 7.2%, p = 0.447), splenectomy (13.1% vs 13.7%, p = 0.846) or nephrectomy (2.0% vs 0.7%, p = 0.229)). Seven out of 25 patients (28.0%) in the warfarin group required further operations after TAE, which was not significantly different from that in the nonwarfarin group (four out of 25 patients, 16.0%, p = 0.306) CONCLUSION: Preinjury warfarin increases the need for TAE but not surgeries. With proper haemostasis with TAE and resuscitation, nonoperative management can still be applied to patients with preinjury warfarin sustaining blunt hepatic, splenic or renal injuries. Patients with preinjury warfarin had a higher risk for surgery after TAE.
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Embolização Terapêutica , Ferimentos não Penetrantes , Humanos , Escala de Gravidade do Ferimento , Estudos Retrospectivos , Baço/lesões , Varfarina/efeitos adversos , Ferimentos não Penetrantes/terapiaRESUMO
Personalized medical care focuses on prediction of disease risk and response to medications. To build the risk models, access to both large-scale genomic resources and human genetic studies is required. The Taiwan Biobank (TWB) has generated high-coverage, whole-genome sequencing data from 1492 individuals and genome-wide SNP data from 103,106 individuals of Han Chinese ancestry using custom SNP arrays. Principal components analysis of the genotyping data showed that the full range of Han Chinese genetic variation was found in the cohort. The arrays also include thousands of known functional variants, allowing for simultaneous ascertainment of Mendelian disease-causing mutations and variants that affect drug metabolism. We found that 21.2% of the population are mutation carriers of autosomal recessive diseases, 3.1% have mutations in cancer-predisposing genes, and 87.3% carry variants that affect drug response. We highlight how TWB data provide insight into both population history and disease burden, while showing how widespread genetic testing can be used to improve clinical care.
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The current human reference genome is predominantly derived from a single individual and it does not adequately reflect human genetic diversity. Here, we analyze 338 high-quality human assemblies of genetically divergent human populations to identify missing sequences in the human reference genome with breakpoint resolution. We identify 127,727 recurrent non-reference unique insertions spanning 18,048,877 bp, some of which disrupt exons and known regulatory elements. To improve genome annotations, we linearly integrate these sequences into the chromosomal assemblies and construct a Human Diversity Reference. Leveraging this reference, an average of 402,573 previously unmapped reads can be recovered for a given genome sequenced to ~40X coverage. Transcriptomic diversity among these non-reference sequences can also be directly assessed. We successfully map tens of thousands of previously discarded RNA-Seq reads to this reference and identify transcription evidence in 4781 gene loci, underlining the importance of these non-reference sequences in functional genomics. Our extensive datasets are important advances toward a comprehensive reference representation of global human genetic diversity.
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Variação Genética , Genoma Humano , População/genética , Mapeamento Cromossômico , Biologia Computacional , Expressão Gênica , Genômica , Técnicas de Genotipagem , Humanos , Anotação de Sequência Molecular , RNA-Seq , Análise de Sequência de DNA , Transcriptoma , Sequenciamento Completo do GenomaRESUMO
Quantifying the density and locating the position of antigens on cell surface has been a challenge in molecular biology research. The challenge lies in the need for a chemically and photophysically stable fluorophore to achieve the required sensitivity and accuracy. Here, we present a method suitable for the purpose by using lipid-encapsulated fluorescent nanodiamonds (FNDs) of 35 nm in diameter as biolabels. The encapsulation of FNDs in biotinylated phospholipids not only facilitates good dispersion of the particles in biological buffers, but also endows them with high specific targeting ability. We demonstrated a viable application of the technique for biotin-mediated immunostaining of antigens on fixed human cells, identifying their positions by two-color confocal fluorescence imaging, and determining their densities by magnetically modulated fluorescence detection. A binding capacity of 6 ± 1 × 104 antigens/cell was measured specifically for CD44 on HeLa cell surface. The result agreed well with the assay of R-phycoerythrin-conjugated antibodies by flow cytometry, supporting the reliability of this new nanoparticle-based method.
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Real-time tracking of membrane proteins is essential to gain an in-depth understanding of their dynamics on the cell surface. However, conventional fluorescence imaging with molecular probes like organic dyes and fluorescent proteins often suffers from photobleaching of the fluorophores, thus hindering their use for continuous long-term observations. With the availability of fluorescent nanodiamonds (FNDs), which have superb biocompatibility and excellent photostability, it is now possible to conduct the imaging in both short and long terms with high temporal and spatial resolution. To realize the concept, we have developed a facile method (e.g., one-pot preparation) to produce alkyne-functionalized hyperbranched-polyglycerol-coated FNDs for bioorthogonal labeling of azide-modified membrane proteins and azide-modified antibodies of membrane proteins. The high specificity of this labeling method has allowed us to continuously monitor the movements of the proteins of interest (such as integrin α5) on/in living cells over 2 h. The results open a new horizon for live cell imaging with functional nanoparticles and fluorescence microscopy.
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Química Click/métodos , Glicoproteínas/química , Proteínas de Membrana/química , Nanodiamantes/química , Imagem Óptica/métodos , Linhagem Celular , Citometria de Fluxo , Células HeLa , Humanos , Microscopia Confocal , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Delayed diagnosis and intervention of blunt bowel and mesenteric injury (BBMI) is a hazard because of poor prognosis. Computed tomography (CT) is the standard imaging tool to evaluate blunt abdominal trauma (BAT). However, a high missed diagnosis rate for BMMI was reported. In this study, we would like to evaluate the presentation of CT in BBMI. Moreover, we want to evaluate the impact of deferred surgical intervention of BBMI on final prognosis. We performed a retrospective study from 2013-2017, including patients with BAT and BBMI who underwent surgical intervention. We evaluated clinical characteristics, CT images, and surgical timing, as well as analyzed the prognosis of BBMI. There were 6164 BAT patients and 188 BMI patients included. The most common characteristics of CT were free fluid (71.3%), free air (43.6%), and mesenteric infiltration (23.4%). There were no single characteristics of a CT image that can predict BBMI significantly. However, under close monitoring, we find that deferred intervention did not prolong the hospital and intensive care unit stays and did not worsen the prognosis and mortality.
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BACKGROUND: Lung squamous cell carcinoma (SCC) cells frequently exhibit markers of chromosome instability such as high fractional allelic loss (FAL). We postulated that alterations in the p53 damage responsive gene and in the double-strand break (DSB) repair genes, BRCA1 and XRCC5, are involved in patients with high FAL. In addition, chromosomal deletion analysis enables the delineation of the likely locations of tumor suppressor genes (TSG) and could provide molecular markers for disease classification. PATIENTS AND METHODS: To define the minimal deletion regions (MDRs), we used 92 microsatellites spanning 29 regions identified in our previous genome-wide chromosomal deletion study in 36 lung SCC patients to verify the maximal contiguous deletion loci. RESULTS: Eight MDRs at 2q35, 3p14.1-3p14.3, 3p22.2-p23, 3p25.3-3p26.3, 5q35.1-q35.2, 9p23-p24.1, 13q14.11-q14.2, and 17p13.1-p13.2 were found in lung SCC. The candidate genes GAS7 and OVCA2 in the MDR17pA (17p13.1-p13.2) were further examined for mRNA expression. Low expression of the GAS7 gene in 57% of patients analyzed suggested its importance in lung SCC tumorigenesis. In addition, we found a panel of five microsatellites (D3S1766, D4S2397, D4S2361, D13S175, and D17S974), which can be used as prognostic biomarkers in lung SCC. Furthermore, alteration in more than two genes in DSB repair-related pathways was more apparent in high FAL patients. CONCLUSIONS: Our results provide biomarkers that may be used for monitoring tumor progression and for positional cloning of new TSGs. Importantly, our data show direct evidence that alterations in DSB repair-related pathways are involved in the genomic instability verified by intensive microsatellites of lung SCC.
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Carcinoma de Células Escamosas/genética , Genes Supressores de Tumor , Perda de Heterozigosidade , Neoplasias Pulmonares/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/cirurgia , Quebras de DNA de Cadeia Dupla , DNA Helicases , Reparo do DNA , Feminino , Genes BRCA1 , Genes p53 , Humanos , Autoantígeno Ku , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
Cationic polymers are often employed in conjugation with nanomaterials, and the resultant hybrids are useful for various bioapplications. Here, a single-step metal-free method for the synthesis of fluorescent nanodiamonds (FNDs) conjugated with cationic polymer brushes is reported. Distinct from the common methods such as atom transfer radical polymerization and reversible addition fragmentation chain transfer, our ring-opening-polymerization-based method is simple and less time consuming and hazardous. Infrared spectroscopy, thermogravimetric analysis, zeta potential, and dynamic light scattering confirmed the synthesis. The produced FND-polymer brushes showed markedly higher cell labeling and internalization efficiency without noticeable cytotoxicity. Our method is general and applicable to other nanoparticles as well for uses in diverse research areas.
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BACKGROUND: Blunt pericardial effusion (BPE) in trauma patients can be suggestive of injuries to the heart or great vessels. Surgical exploration is the mainstay of management; however, the effectiveness of non-operative management in this patient group remains unclear. METHODS: Patients presenting with BPE in the trauma registry system at our level I trauma center were reviewed. Patients with and without cardiovascular (CVS) injury were compared to identify predictors for CVS injury and to understand the factors related to the requirement for surgery. Patients with and without CVS injury who presented with stable hemodynamics and initially received conservative management were also compared. RESULTS: Thirty patients were enrolled in the study with a mean age of 53.2 (standard deviation (SD) 18.0) years and a mean injury severity score (ISS) of 26.7 (SD 9.0). Eleven patients presented with systolic blood pressure (SBP)<100mmHg, and immediate surgical intervention was performed. Eight patients had evidence of CVS injury (73%). Nineteen patients had stable hemodynamics and initially received conservative treatment. Of these, twelve patients received further surgical interventions, and only three had evidence of CVS injury (16%, 3/19). Comparisons of individuals with and without CVS injury revealed that the SBP on presentation was higher in patients without CVS injury than in those with CVS injury (132.7 (SD 41.3) mmHg vs. 95.6 (SD 21.1) mmHg). Clinically irrelevant differences between the two groups were observed for the creatine kinase (CK)-MB level, the troponin I level, the presence of an echocardiography tamponade sign, associated chest trauma and ISS. No remarkable predictors for CVS injury were found in hemodynamically stable patients. CONCLUSION: Non-operative management can be considered for patents with traumatic BPE and stable hemodynamics; however, this approach must be performed at an institution with adequate facilities and well-trained staff.
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Tratamento Conservador , Ecocardiografia , Derrame Pericárdico/etiologia , Centros de Traumatologia , Ferimentos não Penetrantes/complicações , Adulto , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/terapia , Estudos Retrospectivos , Fatores de Risco , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/terapiaRESUMO
Highly stable lipid-encapsulated fluorescent nanodiamonds (FNDs) are produced by photo-crosslinking of diacetylene-containing lipids physically attached to the FND surface. Not only is this coating method simple and fast, but also it gives the FND-lipid hybrids favorable properties for bioapplications. The hybrids are useful as fluorescent biolabels as well as fiducial markers for correlative light and electron microscopy.
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Acetileno/química , Corantes Fluorescentes/química , Lipídeos/química , Nanodiamantes/química , Imagem Óptica , Acetileno/análogos & derivados , Reagentes de Ligações Cruzadas/química , Células HeLa , Humanos , Microscopia Eletrônica de Varredura , Estrutura MolecularRESUMO
Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12â nm and a temporal resolution of 50â ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (â¼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.
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Doença de Alzheimer , Transtorno Autístico , Rastreamento de Células/métodos , Hipocampo , Nanodiamantes/química , Neurônios , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Transporte Biológico Ativo/genética , Células Cultivadas , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência/métodos , Microscopia de Vídeo/métodos , Neurônios/metabolismo , Neurônios/patologiaRESUMO
BACKGROUND: Several unfavorable prognostic factors have been proposed for peripheral cholangiocarcinoma (PCC) in patients undergoing hepatectomy, including gross type of tumor, vascular invasion, lymph node metastasis, a high carbohydrate antigen 19-9 level, and a positive resection margin. However, the clinical effect of a positive surgical margin on the survival of patients with PCC after hepatectomy still needs to be clarified due to conflicting results. METHODS: A total of 224 PCC patients who underwent hepatic resection with curative intent between 1977 and 2007 were retrospectively reviewed. Eighty-nine patients had a positive resection margin, with 62 having a microscopically positive margin and 27 a grossly positive margin (R2). The clinicopathological features, outcomes, and recurrence pattern were compared with patients with curative hepatectomy. RESULTS: PCC patients with hepatolithiasis, periductal infiltrative or periductal infiltrative mixed with mass-forming growth, higher T stage, and more advanced stage tended to have higher positive resection margin rates after hepatectomy. PCC patients who underwent curative hepatectomy had a significantly higher survival rate than did those with a positive surgical margin. When PCC patients underwent hepatectomy with a positive resection margin, the histological grade of the tumor, nodal positivity, and chemotherapy significantly affected overall survival. Locoregional recurrence was the most common pattern of recurrence. CONCLUSION: A positive resection margin had an unfavorable effect on overall survival in PCC patients undergoing hepatectomy. In these patients, the prognosis was determined by the biology of the tumor, including differentiation and nodal positivity, and chemotherapy increased overall survival.
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Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Low-dimensional carbon-based nanomaterials have recently received enormous attention for biomedical applications. However, increasing evidence indicates that they are cytotoxic and can cause inflammatory responses in the body. Here, we show that monocrystalline nanodiamonds (NDs) synthesized by high-pressure-high-temperature (HPHT) methods and purified by air oxidation and strong oxidative acid treatments have excellent hemocompatibility with negligible hemolytic and thrombogenic activities. Cell viability assays with human primary endothelial cells suggested that the oxidized HPHT-NDs (dimensions of 35-500â nm) are non-cytotoxic. No significant elevation of the inflammatory cytokine levels of IL-1ß and IL-6 was detected in mice after intravenous injection of the nanocrystals in vivo. Using a hindlimb-ischemia mouse model, we demonstrated that 35-nm NDs after covalent conjugation with polyarginine are useful as a drug delivery vehicle of heparin for prolonged anticoagulation treatment. The present study lays a solid foundation for further therapeutic applications of NDs in biomedicine.
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Diamante/química , Nanopartículas/química , Animais , Anticoagulantes/química , Anticoagulantes/farmacologia , Materiais Biocompatíveis/química , Sobrevivência Celular , Hemólise , Heparina/química , Heparina/farmacologia , Humanos , Teste de Materiais , Camundongos , Nanoconjugados/química , Nanoconjugados/uso terapêutico , Nanoconjugados/ultraestrutura , Nanomedicina/métodos , Nanopartículas/ultraestrutura , Tempo de Tromboplastina Parcial , Tamanho da PartículaRESUMO
BACKGROUND: Nonsmall cell lung cancer (NSCLC) frequently exhibits genomic instability, such as high fractional allelic loss (FAL). Genomic instability may result from unrepaired or misrepaired double-strand breaks (DSBs). The authors of this report postulated that polymorphisms in genes of the nonhomologous end-joining (NHEJ) pathway, which is the major DSB repair pathway in mammalian cells, may modulate lung cancer susceptibility and prognosis. METHODS: Patients with NSCLC (n = 152) and a group of appropriate age-matched and sex-matched controls (n = 162) were subjected to genotype analysis of the NHEJ pathway genes x-ray repair complementing defective repair in Chinese hamster cells 6 (Ku70) (reference single nucleotide polymorphism number [rs] 2267437), x-ray repair complementing defective repair in Chinese hamster cells 5 (Ku80) (rs3835), x-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) (rs1805377), and DNA ligase IV (LIG4) (rs1805388). The gene-gene interaction (joint effect), genotype-environmental (ie, smoking) correlation, and genotype-phenotype (ie, FAL) correlation were examined. The Kaplan-Meier method and log-rank tests were used to assess the prognostic effect. RESULTS: There was a significant association between the XRCC4 and LIG4 genotypes with NSCLC risk in an analysis of individual polymorphism associations, and the risk of NSCLC increased further in a combined analysis of multiple polymorphisms (adjusted odds ratio [OR], 8.74). The patients who had a homozygous variant guanine/guanine genotype of the XRCC4 gene had a poorer prognosis compared with other patients (P = .015). There was a significant difference between the patient smokers and controls for XRCC4 (adjusted OR, 2.67) and LIG4 (adjusted OR, 2.04). In addition, polymorphisms in XRCC4 and LIG4 were linked significantly with patients who had high FAL (adjusted OR, 2.03-3.84). CONCLUSIONS: To the authors' knowledge, this is the first nested case-control study to demonstrate a significant association between the polymorphisms of genes in the NHEJ pathway and lung cancer susceptibility and prognosis. The results may be useful for risk assessment and disease monitoring of patients with NSCLC.