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We study the spectral zeta functions of the Laplacian on fractal sets which are locally self-similar fractafolds, in the sense of Strichartz. These functions are known to meromorphically extend to the entire complex plane, and the locations of their poles, sometimes referred to as complex dimensions, are of special interest. We give examples of locally self-similar sets such that their complex dimensions are not on the imaginary axis, which allows us to interpret their Laplacian determinant as the regularized product of their eigenvalues. We then investigate a connection between the logarithm of the determinant of the discrete graph Laplacian and the regularized one.
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The problem of reconstructing multiple objects from the average of their diffracted intensities is investigated. Reconstruction feasibility (uniqueness) depends on the number of objects, their support shapes and dimensionality, and an appropriately calculated constraint ratio. For objects with sufficiently different supports, and a favorable constraint ratio, the reconstruction problem has a unique solution. For objects with identical supports, there can be multiple solutions, even with a favorable constraint ratio. However, positivity of the objects and noncentrosymmetry of the support reduce the number of multiple solutions, and a unique solution may exist with a favorable constraint ratio. An iterative projection based algorithm to reconstruct the individual objects is described. The efficacy of the reconstruction algorithm and the uniqueness results are demonstrated by simulation.
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Nanocrystals with more than one molecule in the unit cell will generally crystallize with incomplete unit cells on the crystal surface. Previous results show that the ensemble-averaged diffraction by such crystals consists of a usual Bragg component and two other Bragg-like components due to the incomplete unit cells. Using an intrinsic flexibility in the definition of the incomplete-unit-cell part of a crystal, the problem is formulated such that the magnitude of the Bragg-like components is minimized, which leads to a simpler and more useful interpretation of the diffraction. Simulations show the nature of the relative magnitudes of the diffraction components in different regions of reciprocal space and the effect of crystal faceting.
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Luz , Modelos Químicos , Nanopartículas/química , Nanopartículas/ultraestrutura , Refratometria/métodos , Espalhamento de Radiação , Simulação por Computador , CristalizaçãoRESUMO
Aderamastat (FP-025) is a small molecule, selective matrix metalloproteinase (MMP)-12 inhibitor, under development for respiratory conditions which may include chronic inflammatory airway diseases and pulmonary fibrosis. To support evaluation of the pharmacokinetic parameters of Aderamastat in humans, we developed and validated a high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analytical method for the quantification of Aderamastat in human plasma. This assay was validated in compliance with the Food and Drug Administration (FDA) Good Laboratory Practice Regulations (GLP) and European Medicines Agency (EMA) guidelines. K2EDTA human plasma samples were spiked with internal standard, processed by liquid-liquid extraction, and analyzed using reversed-phase HPLC with Turbo Ion Spray® MS/MS detection. Separation was done using a chromatographic gradient on 5 µm C6-Phenyl 110 Å, 50*2 mm analytical column at a temperature of 35 °C. The LC-MS/MS bioanalytical method, developed by QPS Taiwan to determine the concentration of Aderamastat in K2EDTA human plasma, was successfully validated with respect to linearity, sensitivity, accuracy, precision, dilution, selectivity, hemolyzed plasma, lipemic plasma, batch size, recovery, matrix effect, and carry-over. These data indicate that the method for determination of Aderamastat concentrations in human K2EDTA plasma can be used in pharmacokinetics studies and subsequent clinical trials with Aderamastat. Authors declare that, this novel data is not published and not under consideration for publication by another journal than this journal. All data will be made available on request.
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BACKGROUND: Stereotactic body radiation therapy (SBRT) is known to modulate the immune system and contribute to the generation of anti-tumor T cells and stimulate T cell infiltration into tumors. Radiation-induced immune suppression (RIIS) is a side effect of radiation therapy that can decrease immunological function by killing naive T cells as well as SBRT-induced newly created effector T cells, suppressing the immune response to tumors and increasing susceptibility to infections. PURPOSE: RIIS varies substantially among patients and it is currently unclear what drives this variability. Models that can accurately predict RIIS in near real time based on treatment plan characteristics would allow treatment planners to maintain current protocol specific dosimetric criteria while minimizing immune suppression. In this paper, we present an algorithm to predict RIIS based on a model of circulating blood using early stage lung cancer patients treated with SBRT. METHODS: This Python-based algorithm uses DICOM data for radiation therapy treatment plans, dose maps, patient CT data sets, and organ delineations to stochastically simulate blood flow and predict the doses absorbed by circulating lymphocytes. These absorbed doses are used to predict the fraction of lymphocytes killed by a given treatment plan. Finally, the time dependence of absolute lymphocyte count (ALC) following SBRT is modeled using longitudinal blood data up to a year after treatment. This model was developed and evaluated on a cohort of 64 patients with 10-fold cross validation. RESULTS: Our algorithm predicted post-treatment ALC with an average error of 0.24 ± 0.21 × 10 9 $0.24 \pm 0.21 \times {10}^9$ cells/L with 89% of the patients having a prediction error below 0.5 × 109 cells/L. The accuracy was consistent across a wide range of clinical and treatment variables. Our model is able to predict post-treatment ALC < 0.8 (grade 2 lymphopenia), with a sensitivity of 81% and a specificity of 98%. This model has a â¼38-s end-to-end prediction time of post treatment ALC. CONCLUSION: Our model performed well in predicting RIIS in patients treated using lung SBRT. With near-real time model prediction time, it has the capability to be interfaced with treatment planning systems to prospectively reduce immune cell toxicity while maintaining national SBRT conformity and plan quality criteria.
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X-ray femtosecond nanocrystallography is a new, potentially powerful technique for imaging biological macromolecules that uses ensemble-averaged measurements of diffraction of x-ray free-electron laser pulses from nanocrytalline specimens. Nanocrystals have some diffraction characteristics that are distinct from those of macroscopic crystals, due to the presence of different kinds of unit cell in the crystal and of truncated unit cells on the crystal surface. Expressions are derived for diffraction by nanocrystals with variable and incomplete unit cells, averaged over a distribution of crystal sizes and shapes. The diffraction contains differently modulated Bragg components that are due to interference effects within and between the full and incomplete unit cells. Estimates are obtained for the relative magnitudes of the components. The nature of the diffraction is illustrated by two-dimensional simulations. Implications for molecular imaging are discussed.
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Nanopartículas/química , Nanotecnologia/métodos , Algoritmos , Simulação por Computador , Cristalografia por Raios X/métodos , Processamento de Imagem Assistida por Computador , Lasers , Método de Monte Carlo , Difração de Raios XRESUMO
BACKGROUND: Ocular complaints, including acute or subacute vision loss, are commonly encountered in emergency departments (ED). These potentially time-sensitive complaints are difficult to diagnose and evaluate without adequate, specialized equipment and expertise. Additionally, a thorough evaluation often requires a more extensive and specialized physical exam, imaging, and ophthalmologic consultation, all of which may not be readily available in the acute setting. CASE PRESENTATION: This case report presented a patient in the emergency department with the chief complaint of vision loss. Point-of-care ultrasound (POCUS) using the 10-MHz-linear-array probe, in the ocular setting, demonstrated calcification of the lens, a finding consistent with cataract in the right eye. CONCLUSIONS: The use of POCUS can expedite the accurate identification of vision threatening pathology, such as cataracts, and streamline ED disposition and plan of care.
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Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Cetuximab/efeitos adversos , Estudos Retrospectivos , Neoplasias Colorretais/tratamento farmacológico , Pontuação de Propensão , Neoplasias do Colo/tratamento farmacológico , Nutrição Parenteral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
This multicenter study aimed to explore the survival benefit of metastasectomy by first-line cetuximab-based chemotherapy in real-world patients with RAS wild-type metastatic colorectal cancer (mCRC). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and metastasectomy rate. The exploratory endpoint was the optimal treatment cycle for better OS and PFS. Receiver operating characteristic curve with the area under curve (AUC) was used to identify the optimal cut-off cycle for survival outcomes. A total of 758 mCRC patients were enrolled in this study, with a median OS of 35.1 months, median PFS of 14.6 months, and metastasectomy rate of 21.4%. Left-sided mCRC had a significantly higher DCR (88.9% vs. 73.1%, P<0.001) and better OS (36.4 vs. 19.6 months, P<0.001). There were no significant differences in PFS and metastasectomy rate between left-sided and right-sided mCRC. However, mCRC patients who underwent metastasectomy over the course of treatment had better OS (54.9 vs. 28.6 months, P<0.001) and PFS (21.0 vs. 13.1 months, P<0.001) than those who did not. Notably, right-sided mCRC who benefited from first-line cetuximab-based chemotherapy to underwent metastasectomy also had favorable outcomes, on a par with left-sided mCRC. The optimal treatment cycle was 14 cycles (AUC: 0.779, P<0.001). Patients who received ≥14 cycles had higher metastasectomy rates (27.5% vs. 13.5%, P<0.001), favorable OS (42.6 vs. 23.4 months, P<0.001) and PFS (18.1 vs. 8.6 months, P<0.001), and, importantly, had comparable adverse events compared with patients who received <14 cycles of treatment. Patients who underwent metastasectomy after or during first-line cetuximab therapy have an improved OS in both left-sided and right-sided mCRC. Furthermore, patients receive ≥14 cycles of treatment whenever possible to achieve a higher likelihood of metastasectomy was associated with favorable survival outcomes.
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INTRODUCTION: Cancer consistently remains one of the top causes of death in the United States every year, with many cancer deaths preventable if detected early. Circulating serum miRNAs are a promising, minimally invasive supplement or even an alternative to many current screening procedures. Many studies have shown that different serum miRNAs can discriminate healthy individuals from those with certain types of cancer. Although many of those miRNAs are often reported to be significant in one cancer type, they are also altered in other cancer types. Currently, very few studies have investigated serum miRNA biomarkers for multiple cancer types for general cancer screening purposes. METHOD: To identify serum miRNAs that would be useful in screening multiple types of cancers, microarray cancer datasets were curated, yielding 13 different types of cancer with a total of 3352 cancer samples and 2809 non-cancer samples. The samples were divided into training and validation sets. One hundred random forest models were built using the training set to select candidate miRNAs. The selected miRNAs were then used in the validation set to see how well they differentiate cancer from normal samples in an independent dataset. Furthermore, the interactions between these miRNAs and their target mRNAs were investigated. RESULT: The random forest models achieved an average of 97% accuracy in the training set with 95% bootstrap confidence interval of 0.9544 to 0.9778. The selected miRNAs were hsa-miR-663a, hsa-miR-6802-5p, hsa-miR-6784-5p, hsa-miR-3184-5p, and hsa-miR-8073. Each miRNA exhibited high area under the curve (AUC) value using receiver operating characteristic analysis. Moreover, the combination of four out of five miRNAs achieved the highest AUC value of 0.9815 with high sensitivity of 0.9773, indicating that these miRNAs have a high potential for cancer screening. miRNA-mRNA and protein-protein interaction analysis provided insights into how these miRNAs play a role in cancer.
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MicroRNA Circulante , MicroRNAs , Neoplasias , Biomarcadores , Humanos , MicroRNAs/genética , Neoplasias/diagnóstico , Neoplasias/genética , RNA Mensageiro/genética , Curva ROCRESUMO
BACKGROUND: In the United States, the prevalence of opioid use disorders has increased in recent years along with an attendant rise in the incidence of chronic pain disorders and prescription opioid use. Patient navigation services have been used to improve health outcomes in cancer and other chronic disease states, but it is unclear whether the implementation of patient navigation services can facilitate improved outcomes among patients receiving chronic opioid therapy. OBJECTIVES: The objective of this study was to compare the outcomes of patients receiving chronic opioid therapy plus patient navigation services and those receiving chronic opioid therapy as a part of usual care. STUDY DESIGN: This was a prospective, observational study. Consecutive patients receiving chronic opioid therapy were enrolled, with alternating assignments to patient navigation (n = 30) or usual care (n = 30). Participants in the patient navigation group received support from a non-physician, non-advanced practice provider staff member who initiated frequent contact via telephone, telemedicine, or in-clinic visits to discuss the patient's health goals. The minimum follow-up period was 90 days. Outcomes qualitatively compared across groups included final pain score, final morphine milligram equivalent (MME) per day, and discharge rates. Risk factors for discharge within the navigation group were assessed. Patient feedback was also solicited. SETTING: This study was conducted at a single independent pain clinic in the United States. RESULTS: Demographic features were similar between the navigator group and the control group. The control group had a higher average initial pain score (7.0/10) than the intervention group (5.9/10) and were receiving a higher initial dose of opioids (23.1 vs 19.0 MME/d). After an average follow-up of 108.7 days, patients in the navigator group had a 16% decrease in final opioid dose compared with a 23% increase in the control group. Furthermore, patients in the control group were discharged from the practice at a higher rate (23.3% vs 6.6%), suggesting increased opioid misuse in the control group compared with the navigator group. In the navigator group, higher levels of anxiety and depression were the primary predictors of discharge. LIMITATIONS: This was a single-center study with a small sample size. The generalizability of these results to other clinic settings is unknown. CONCLUSIONS: Patient navigation decreased opioid use and practice discharge compared with usual care in an independent pain clinic, suggesting a role for patient navigation in reducing opioid misuse and potentially reducing adverse events.
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Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Navegação de Pacientes , Analgésicos Opioides/uso terapêutico , Dor Crônica/induzido quimicamente , Dor Crônica/tratamento farmacológico , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Padrões de Prática Médica , Estudos Prospectivos , Estudos Retrospectivos , Estados UnidosRESUMO
Background: Metabolic syndrome (MetS) encompasses several clinical presentations that include truncal obesity and insulin resistance at its core. MetS afflicts 23% of the adult US population, increasing their risk of diabetes and cardiovascular disease. Many studies have indicated the importance of a vegetarian diet in improving overall health and more specifically MetS components. Unfortunately, these findings have been inconsistent and cannot be extended to examine effects on MetS incidence in the younger adult population. Objective: This study aimed to conduct a retrospective analysis of a vegetarian vs. non-vegetarian dietary status in young adults (age 18-24) based on MetS components in later adulthood (age 20-30). This study focuses on elucidating any relationship between a vegetarian diet and MetS components of central obesity, hypertension, and hyperlipidemia. Methods: Waves 3 and 4 data were acquired from AddHealth. One-to-one propensity score matched vegetarians to non-vegetarians in a cohort of 535 women and 159 men. Logistical regression assessed the relationship between vegetarian status and MetS components, including truncal obesity (cm), hypertension (normal, pre-HT, HT1, and HT2), and hyperlipidemia (high and low). Results MetS components from ages 20 to 30 are not associated with vegetarian dietary status. Truncal obesity [N = 694; M = 92.82 cm; OR 0.999; p = 0.893; 95% CI (0.980, 1.017)]; hypertension [N = 694; OR 0.949; p = 0.638; 95% CI (0.764, 1.179)]; hyperlipidemia [N = 694; OR 0.840; p = 0.581; 95% CI (0.453, 1.559)]. Conclusion: Current study results were consistent with previous findings suggesting that consumption of a vegetarian diet cannot be directly linked to MetS outcomes. However, further investigation should be completed as MetS is a risk factor for several chronic diseases.
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Hipertensão , Síndrome Metabólica , Adolescente , Adulto , Dieta Vegetariana , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Serial femtosecond crystallography (SFX) is a powerful technique that exploits X-ray free-electron lasers to determine the structure of macro-molecules at room temperature. Despite the impressive exposition of structural details with this novel crystallographic approach, the methods currently available to introduce crystals into the path of the X-ray beam sometimes exhibit serious drawbacks. Samples requiring liquid injection of crystal slurries consume large quantities of crystals (at times up to a gram of protein per data set), may not be compatible with vacuum configurations on beamlines or provide a high background due to additional sheathing liquids present during the injection. Proposed and characterized here is the use of an immiscible inert oil phase to supplement the flow of sample in a hybrid microfluidic 3D-printed co-flow device. Co-flow generation is reported with sample and oil phases flowing in parallel, resulting in stable injection conditions for two different resin materials experimentally. A numerical model is presented that adequately predicts these flow-rate conditions. The co-flow generating devices reduce crystal clogging effects, have the potential to conserve protein crystal samples up to 95% and will allow degradation-free light-induced time-resolved SFX.
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The proofreading exonucleases of all DNA replicases contain acidic residues that chelate two Mg(2+) ions that participate in catalysis. DNA polymerase III holoenzymes contain their proofreading activity in a separate subunit, epsilon, which binds the polymerase subunit, alpha, through alpha's N-terminal php domain. Here we demonstrate that the alpha php domain contains a novel Zn(2+)-dependent 3' --> 5' exonuclease that preferentially removes mispaired nucleotides, providing the first example of a coediting nuclease.
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DNA Polimerase Dirigida por DNA/metabolismo , Exonucleases/metabolismo , Zinco/farmacologia , Cátions Bivalentes/química , Estabilidade Enzimática , Subunidades Proteicas/metabolismo , Thermus thermophilus/efeitos dos fármacos , Thermus thermophilus/enzimologia , Zinco/químicaRESUMO
BACKGROUND: Castleman's disease (CD) is a rare, benign lymphoproliferative disorder that can involve single lymph node stations or can be systemic. Unicentric CD in patients with microcytic anemia is rarely described in the English literature. CASE REPORT: We describe the case of a 19-year-old Chinese woman with hyaline vascular type of unicentric CD presenting as severe non-iron deficiency microcytic anemia. We report the clinical course from the initial presentation to diagnosis and surgical cure, and discuss the most up-to-date information on CD. CONCLUSIONS: CD should be included in the differential diagnosis of microcytic anemia. Imaging tools and pathological studies should be considered in order to make a more accurate diagnosis and to avoid the use of ineffective treatments.
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Anemia Hipocrômica/diagnóstico , Anemia Hipocrômica/cirurgia , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/cirurgia , Diagnóstico Diferencial , Feminino , Hemoglobinometria , Humanos , Linfonodos/patologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Lung cancer is one of the deadliest cancers in the world. Two of the most common subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), have drastically different biological signatures, yet they are often treated similarly and classified together as non-small cell lung cancer (NSCLC). LUAD and LUSC biomarkers are scarce, and their distinct biological mechanisms have yet to be elucidated. To detect biologically relevant markers, many studies have attempted to improve traditional machine learning algorithms or develop novel algorithms for biomarker discovery. However, few have used overlapping machine learning or feature selection methods for cancer classification, biomarker identification, or gene expression analysis. This study proposes to use overlapping traditional feature selection or feature reduction techniques for cancer classification and biomarker discovery. The genes selected by the overlapping method were then verified using random forest. The classification statistics of the overlapping method were compared to those of the traditional feature selection methods. The identified biomarkers were validated in an external dataset using AUC and ROC analysis. Gene expression analysis was then performed to further investigate biological differences between LUAD and LUSC. Overall, our method achieved classification results comparable to, if not better than, the traditional algorithms. It also identified multiple known biomarkers, and five potentially novel biomarkers with high discriminating values between LUAD and LUSC. Many of the biomarkers also exhibit significant prognostic potential, particularly in LUAD. Our study also unraveled distinct biological pathways between LUAD and LUSC.
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Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Biomarcadores/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/genética , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Técnicas Genéticas , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Masculino , PrognósticoRESUMO
The Ames dwarf (df/df) mouse is a well-established model for delayed aging. MicroRNAs (miRNAs), the most studied small noncoding RNAs (sncRNAs), may regulate ovarian aging to maintain a younger ovarian phenotype in df/df mice. In this study, we profile other types of ovarian sncRNAs, PIWI-interacting RNAs (piRNAs) and piRNA-like RNAs (piLRNAs), in young and aged df/df and normal mice. Half of the piRNAs derive from transfer RNA fragments (tRF-piRNAs). Aging and dwarfism alter the ovarian expression of these novel sncRNAs. Specific tRF-piRNAs that increased with age might target and decrease the expression of the breast cancer antiestrogen resistance protein 3 (BCAR3) gene in the ovaries of old df/df mice. A set of piLRNAs that decreased with age and map to D10Wsu102e mRNA may have trans-regulatory functions. Other piLRNAs that decreased with age potentially target and may de-repress transposable elements, leading to a beneficial impact on ovarian aging in df/df mice. These results identify unique responses in ovarian tissues with regard to aging and dwarfism. Overall, our findings highlight the complexity of the aging effects on gene expression and suggest that, in addition to miRNAs, piRNAs, piLRNAs, tRF-piRNAs, and their potential targets can be central players in the maintenance of a younger ovarian phenotype in df/df mice.
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Envelhecimento/genética , Longevidade/genética , Ovário/metabolismo , RNA Interferente Pequeno/metabolismo , Pequeno RNA não Traduzido/metabolismo , Animais , Nanismo Hipofisário/genética , Feminino , Camundongos , Camundongos Knockout , Oogênese/genética , FenótipoRESUMO
BACKGROUND: En bloc right hemicolectomy plus pancreaticoduodenectomy (PD) is administered for locally advanced colon carcinoma that invades the duodenum and/or pancreatic head. This procedure may also be called colo-pancreaticoduodenectomy (cPD). Patients with such carcinomas may present with acute abdomen. Emergency PD often leads to high postoperative morbidity and mortality. Here, we aimed to evaluate the feasibility and outcomes of emergency cPD for patients with advanced colon carcinoma manifesting as acute abdomen. METHODS: We retrospectively reviewed 4898 patients with colorectal cancer who underwent curative colectomy during the period from 1994 to 2018. Among them, 30 had locally advanced right colon cancer and had received cPD. Among them, surgery was performed in 11 patients in emergency conditions (bowel obstruction: 6, perforation: 3, tumor bleeding: 2). Selection criteria for emergency cPD were the following: (1) age ≤ 60 years, (2) body mass index < 35 kg/m2, (3) no poorly controlled comorbidities, and (4) perforation time ≤ 6 h. Three patients did not meet the above criteria and received non-emergency cPD after a life-saving diverting ileostomy, followed by cPD performed 3 months later. We analyzed these patients in terms of their clinicopathological characteristics, the early and long-term postoperative outcomes, and compared findings between emergency cPD group (e-group, n = 11) and non-emergency cPD group (non-e-group, n = 19). After cPD, staged pancreaticojejunostomy was performed in all e-group patients, and on 15 of 19 patients in the non-e-group. RESULTS: The non-e-group was older and had a higher incidence of associated comorbidities, while other clinicopathological characteristics were similar between the two groups. None of the patients in the two groups succumbed from cPD. The postoperative complication rate was 63.6% in the e-group and 42.1% in the non-e-group (p = 0.449). The 5-year overall survival rate were 15.9% in the e-group and 52.6% in the non-e-group (p = 0.192). CONCLUSIONS: Emergency cPD is feasible in highly selected patients if performed by experienced surgeons. The early and long-term positive outcomes of emergency cPD are similar to those after non-emergency cPD in patients with acute abdominal conditions.
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Abdome Agudo/cirurgia , Colectomia , Neoplasias do Colo/cirurgia , Pancreaticoduodenectomia , Abdome Agudo/patologia , Adulto , Idoso , Neoplasias do Colo/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologiaRESUMO
Typically, biochemical screens that employ pure macromolecular components focus on single targets or a small number of interacting components. Researches rely on whole cell screens for more complex systems. Bacterial DNA replicases contain multiple subunits that change interactions with each stage of a complex reaction. Thus, the actual number of targets is a multiple of the proteins involved. It is estimated that the overall replication reaction includes up to 100 essential targets, many suitable for discovery of antibacterial inhibitors. We have developed an assay, using purified protein components, in which inhibitors of any of the essential targets can be detected through a common readout. Use of purified components allows each protein to be set within the linear range where the readout is proportional to the extent of inhibition of the target. By performing assays against replicases from model Gram-negative and Gram-positive bacteria in parallel, we show that it is possible to distinguish compounds that inhibit only a single bacterial replicase from those that exhibit broad spectrum potential.
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Bactérias/enzimologia , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/farmacologia , Inibidores da Síntese de Ácido Nucleico , Replicação do DNA/efeitos dos fármacos , DNA Bacteriano/biossíntese , DNA Polimerase Dirigida por DNA , Inibidores Enzimáticos/química , Ensaios de Triagem em Larga Escala , Humanos , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Especificidade por SubstratoRESUMO
BACKGROUND: Pelvic irradiation is commonly used in the treatment of pelvic malignancies. Chronic radiation enterocolitis is the most serious complication resulting from such treatment, and it frequently requires surgery. The prognosis for patients after surgery remains ill-defined. We conducted a retrospective study to identify risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis. METHODS: From 1985 to 2009, a total of 89 patients were diagnosed as having chronic radiation enterocolitis in Taichung Veterans General Hospital. The chart records of 35 surgical and 54 nonsurgical patients were reviewed. A total of 21 candidate risk factors were selected from (1) those related to rapid disease progression (recurrence within 1 year, reoperation within 1 year, short latency), (2) those mentioned in published series (diabetes mellitus, history of smoking, history of abdominopelvic surgery), and (3) other risk factors that might adversely affect outcomes (older age, higher radiation dosage, longer latency period). Factors with p < 0.1 in univariate analysis were subjected to multivariate analysis to identify those that were independent risk factors. RESULTS: Surgical patients were significantly older (65.09 vs. 61.61 years, p = 0.011), had a longer latency period (17.08 vs. 8.09 months, p = 0.037), and were associated with a higher percentage of radiation uropathy (54.28 vs. 12.96%, p < 0.0001) than nonsurgical patients. There was no difference in radiation dosage between surgical and nonsurgical cases (p = 0.152). Recurrence of radiation enterocolitis within 1 year following surgery (p = 0.022), older age (p = 0.002), and uncured cancer (p = 0.001) were identified as independent risk factors for poor overall survival after surgery. All patients (100%) who had recurrent radiation enterocolitis within 1 year of surgery died within 5 years of recurrence. CONCLUSIONS: The surgical cases were older, had a longer latency period, and had a higher percentage of radiation uropathy .Recurrence of radiation enterocolitis within 1 year after surgery, older age, and uncured cancer were independent risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis.