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1.
Phys Rev Lett ; 128(24): 244801, 2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35776476

RESUMEN

The efficiency of high-order harmonic generation from a relativistic laser interacting with solid targets depends greatly on surface plasma distribution. The usual method of enhancing efficiency involves tuning the plasma scale length carefully by improving the laser contrast. Here, we experimentally demonstrate that efficient harmonics can be achieved directly by compressing large-scale surface plasma via the radiation pressure of a circularly polarized normally incident prepulse. The harmonic generation efficiency obtained by this method is comparable to that obtained with optimized plasma scale length by high-contrast lasers. Our scheme does not rely on high-contrast lasers and is robust and easy to implement. Thus, it may pave a way for the development of intense extreme ultraviolet sources and future applications with high repetition rates.

2.
Ultrasonics ; 125: 106773, 2022 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-35688013

RESUMEN

The use of guided waves to identify damage has become a popular method due to its robustness and fast execution, as well as the advantage of being able to inspect large areas and detect minor structural defects. When a travelling wave on a plate interacts with a defect, it generates a scattered field that will depend on the defects geometry. By analysing the scattered field, one can thus characterize the type and size of the plate damage. A Bayesian framework based on a guided waves interaction model for damage identification of infinite plate for the first time is presented here. A semi-analytical approach based on the lowest order plate theories is adopted to obtain the scattering features for damage geometries with circular symmetry, resulting in an efficient inversion procedure. Subsequently, ultrasound experiments are performed on a large aluminium plate with a circular indentation to generate wave reflection and transmission coefficients. With the aid of signal processing techniques, the effectiveness and efficiency of the proposed approach are verified. A full finite element model is used to test the damage identification scheme. Finally, the scattering coefficients are reconstructed, reliably matching the experimental results. The framework supports digital twin technology of structural health monitoring.

3.
Zhonghua Nei Ke Za Zhi ; 61(7): 801-805, 2022 Jul 01.
Artículo en Chino | MEDLINE | ID: mdl-35764565

RESUMEN

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population (P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls (P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients (P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively (P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).


Asunto(s)
Mieloma Múltiple , Aberraciones Cromosómicas , Humanos , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos
4.
Zhonghua Zhong Liu Za Zhi ; 44(6): 562-569, 2022 Jun 23.
Artículo en Chino | MEDLINE | ID: mdl-35754231

RESUMEN

Objective: To investigate the correlation of homocysteine (HCY) and coagulation function index with the risk of breast cancer and its clinicopathological characteristics. Methods: The HCY, coagulation function test index, and clinicopathological information of female breast cancer patients (333 cases) treated in Tianjin Medical University Cancer Hospital from January 2018 to December 2018 were collected, and female patients with benign breast (225 cases) were selected during the same period for the control group. The t-test was used to compare measurement data with normal distribution, D-Dimer data were distributed discreetly and described by median, non-parametric Mann-Whitney U test was used to compare the two groups. The chi-square test was used to compare enumeration data, and the Logistic regression analysis was used for the risk analysis. Results: The levels of HCY, fibrinogen (Fbg), protein C (PC), and median D-Dimer (D-D) in peripheral blood of breast cancer patients group [(13.26±5.24) µmol/L, (2.61±0.83) g/L, (117.55±19.67)%, and 269.68 ng/ml, respectively] were higher than those in the control group [(11.58±0.69) µmol/L, (2.49±0.49) g/L, (113.42±19.82)% and 246.98 ng/ml, respectively, P<0.05]. The prothrombin time (PT), PT(INR), α2-antiplasmin (α2-AP) levels [(10.19±0.63) s, 0.91±0.07 and (110.64±13.93)%, respectively] were lower than those in the control group [(10.58±0.65) s, 0.93±0.01 and (123.81±14.77) %, P<0.05]. The serum levels of PC and median D-D in premenopausal breast cancer patients [(112.57±17.86)% and 242.01 ng/ml, respectively] were higher than those in the control group [(105.31±22.31)% and 214.75 ng/ml, respectively, P<0.05]. The levels of PT(INR), α2-AP [0.91±0.07 and (111.29±12.54)%, respectively] were lower than those of the control group[0.98±0.15 and (120.17±16.35)%, respectively, P<0.05]. The levels of HCY and median D-D in postmenopausal breast cancer patients [(14.25±5.76) µmol/L and 347.53 ng/ml, respectively] were higher than those in the control group [(11.67±2.38) µmol/L and 328.28 ng/ml, P<0.05]. The levels of PT, PT(INR), antithrombin Ⅲ (AT-Ⅲ), α2-AP levels [(10.18±0.66) s, 0.87±0.09, (97.30±12.84)% and (110.13±14.96)%] were lower than those in the control group [(10.38±0.61) s, 0.90±0.08, (102.89±9.12)%, and (127.05±12.38)%, respectively, P<0.05]. The levels of α2-AP and median D-D in T2-4 stage breast cancer patients [(111.69±14.41)% and 289.25 ng/ml, respectively] were higher than those in Tis-1 stage patients [(108.05±12.37)% and 253.49 ng/ml, respectively, P<0.05]. The levels of PT, PT (INR), Fbg, AT-Ⅲ, α2-AP, median D-D [(10.62±0.63) s, 0.95±0.06, (3.04±1.52) g/L, (103.21±9.45)%, (118.72±14.77)% and 331.33 ng/ml, respectively] in breast cancer patients with lymph node metastasis were higher than those of patients without lymph node metastasis [(10.42±0.58) s, 0.93±0.06, (2.52±0.54) g/L, (95.20±13.63)%, (106.91±13.13)% and 263.38 ng/ml, respectively, P<0.05]. In non-menopausal breast cancer patients, the level of HCY [(12.63±4.41) µmol/L] in patients with T2-4 stage was higher than that of patients with Tis-1 stage [(10.70±3.49) µmol/L, P=0.010], and the level of thrombin time [(19.35±0.90) s] of patients with T2-4 stage was lower than that of patients with Tis-1 stage [(19.79±1.23) s, P=0.015]. The levels of PT(INR), Fbg, AT-Ⅲ, α2-AP [0.97±0.56, (3.37±2.34) g/L, (102.38±8.77)% and (120.95±14.06)%] in patients with lymph node metastasis were higher than those of patients without lymph node metastasis [0.94±0.05, (2.36±0.48) g/L, (94.56±14.37)% and (109.51±11.46)%, respectively, P<0.05]. Among postmenopausal breast cancer patients, the levels of AT-Ⅲ and α2-AP in T2-4 stage patients [(98.48±11.80)% and (111.84±15.35)%, respectively] were higher than those in patients with the Tis-1 stage [(94.12±14.98)% and (105.49±12.89)%, respectively, P<0.05]. The levels of AT-Ⅲ and α2-AP in N1-3 stage patients [(103.74±9.94)% and (117.29±15.23)%] were higher than those in N0 stage patients [(95.75±13.01)% and (108.39±14.42)%, P<0.05]. Conclusions: HCY and abnormal coagulation function are related to the risk of breast cancer, T stage and lymph node metastasis in breast cancer patients.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Neoplasias de la Mama , Femenino , Fibrinógeno/metabolismo , Homocisteína , Humanos , Metástasis Linfática , Tiempo de Protrombina
5.
Artículo en Inglés | MEDLINE | ID: mdl-35490383

RESUMEN

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is characterized by diffuse hyperkeratosis affecting palms and soles with suprabasal epidermolysis or vacuolar degeneration histopathologically. The disorder is caused by heterozygous mutations in KRT9 or KRT1. Dominant-negative mutations in KRT1 could also result in epidermolytic ichthyosis with EPPK, a more severe entity affecting the entire body. OBJECTIVE: To investigate the genetic basis and pathogenesis of two unrelated patients with EPPK and knuckle pads, both of whom were born to consanguineous parents of Chinese origin. METHODS: Next-generation sequencing was applied to the two patients using genomic DNA extracted from peripheral blood. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence (IF) staining and Western blot (WB) were employed to evaluate mRNA and protein expression level. Ultrastructural changes of skin lesion were analysed using transmission electron microscopy. RESULTS: Two novel homozygous mutations, c.457C > T (p.Gln153*) and c.33C > G (p.Tyr11*) in KRT1, were identified in patients 1 and 2 respectively. The nonsense mutations were predicted to result in nonsense-mediated mRNA decay and absence of keratin 1, which was confirmed in the skin lesions from patient 1. Upregulated keratin 2 was detected both in the affected and unaffected skin samples from patient 1, while the protein abundance and distribution pattern of keratin 10 remained unchanged. An aberrant and clumped staining pattern of keratin 9 was noted in the palmar skin of patient 1. CONCLUSIONS: Homozygous 'knockout' mutations in KRT1 resulted in EPPK with knuckle pads rather than epidermolytic ichthyosis. We speculated that sparing of non-acral skin might be due to compensatory effect of keratin 2 upregulation by forming heterodimer with keratin 10.

6.
Rev Sci Instrum ; 93(3): 033702, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35365019

RESUMEN

A high-speed radiation imaging system based on an image converter of liquid scintillator filled capillary arrays has been developed, which is sensitive to x rays, gamma rays, and neutrons. This imaging system has advantages of both high spatial resolution and high sensitivity because increasing the thickness of the image converter only leads to little deterioration on imaging resolution. The capillary arrays have dimensions of 150 mm diameter and 50 mm thickness, with 100 µm diameter of each capillary. The fluorescence decay time of the filled liquid scintillator based on the mixture of p-xylene and 2,5-diphenyloxazole has been evaluated to be ∼3 ns with the single photon method under the gamma ray excitation. The spatial resolution has been experimentally evaluated to be about 1.15 and 0.6 mm, under excitation of x rays and neutrons, respectively. The imaging system has been applied for diagnosing the dynamic x-ray spot generated by the rod pinch. Two frames in single shot with 15 ns temporal resolution and 20 ns inter-frame separation time have been obtained, which show the spatiotemporal distribution of the electrons bombarding the tungsten rod, indicating the ability of this imaging system in diagnosing dynamic radiation objects. In addition, the technique of capillary arrays provides a promising path for applications of advanced liquid scintillators in the field of radiation imaging.

7.
Artículo en Chino | MEDLINE | ID: mdl-35439856

RESUMEN

Objective: To investigate the effect and underlying mechanism of paeoniflorin on hippocampal neuron apoptosis induced by lead acetate. Methods: In September 2020, primary hippocampal neuronal cells were isolated and cultured from fetal rats, and identified using cellular immunofluorescent. MTT assay was used to measure the cell viability to determine the concentration and time of lead acetate-induced hippocampal neuron apoptosis. MTT was also used to evaluate the effect of paeoniflorin concentration on the apoptosis of hippocampal neurons induced by lead acetate. According to the results, different concentrations of paeoniflorin were selected to intervene hippocampal neuron cells, after 24 h, lead acetate was added to the cells, meanwhile, blank and model groups were set up, the content of reactive oxygen species (ROS) , superoxide dismutase (SOD) , lactate dehydrogenase (LDH) , malondialdehyde (MDA) and Caspase-3 were measured. Extracellular signal regulated kinase (ERK) , phosphorylated ERK (p-ERK) , p38 mitogen -activated protein kinases (p38MAPK) , phosphorylated p38MAPK (p-p38MAPK) , c-Jun N-terminal kinase (JNK) and phosphorylated JNK (p-JNK) protein expression in hippocampal neuronal cells were determined by Western blotting. Results: The isolated and cultured hippocampal neurons were identified by immunofluorescence chemical staining and then treated with lead acetate, MTT results showed that lead acetate had the best toxicity effect when treated for 24 h at a concentration of 25 µmol/L. Paeoniflorin showed no cytotoxic effect on hippocampal neuronal cells when the concentrations below 80 µmol/L. Compared with the model group, the activity of hippocampal neuronal cells was significantly increased after treating with 20, 40 or 80 µmol/L paeoniflorin (P<0.05) . Compared with the blank group, the ROS activity, LDH release level, MDA content and caspase-3 content were significantly increased (P<0.01) , and the SOD activity was significantly decreased (P< 0.01) in the hippocampal neuronal cells of the model group. Compared with the model group, the ROS activity, LDH release level, MDA content and caspase-3 content were obviously decreased (P<0.05) , SOD activity was significantly increased (P <0.01) after hippocampal neuronal cells were treated with 40 or 80 µmol/L paeoniflorin. Relative to the model group, the ratio of p-ERK/ERK were significantly up-regulated (P<0.01) , while the ratios of p-p38MAPK/p38MAPK and p-JNK/JNK were significantly down-regulated after hippocampal neuronal cells were treated with 40 or 80 µmol/L paeoniflorin (P<0.05) . Conclusion: Paeoniflorin may down-regulate the expression of p-p38MAPK and p-JNK protein, up-regulate the expression of p-ERK protein, and inhibit the apoptosis of hippocampal neurons induced by lead acetate through the MAPK signaling pathway.


Asunto(s)
Hipocampo , Plomo , Acetatos/metabolismo , Acetatos/farmacología , Animales , Apoptosis , Caspasa 3/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucósidos , Hipocampo/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/farmacología , Monoterpenos , Neuronas/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
8.
J Occup Environ Hyg ; : 1-8, 2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35452589

RESUMEN

A small pilot study was conducted to test whether the technique of in vivo neutron activation analysis could measure bone aluminum levels in 15 miners who had been exposed to McIntyre Powder over 40 years prior. All miners were over 60 years of age, had worked in mines that used McIntyre Powder, and were sufficiently healthy to travel from northern to southern Ontario for the measurements. Individual aluminum levels were found to be significantly greater than zero with 95% confidence (p < 0.05) in 7 out of the 15 miners. The inverse variance weighted mean of the 15 participants was 21.77 ± 2.27µgAl/gCa. This was significantly higher (p < 0.001) than in a group of 15 non-occupationally exposed subjects of a comparable age from Southern Ontario who had been measured in a previous study. The inverse variance weighted mean bone aluminum content in the non-occupationally exposed group was 3.51 ± 0.85µgAl/gCa. Since the use of McIntyre Powder ceased in 1979, these subjects had not been exposed for more than 40 years. Calculations of potential levels at the cessation of exposure in the 1970s, using a biological half-life of aluminum in bone of 10 to 20 years predicted levels of bone aluminum comparable with studies performed in dialysis patients in the 1970s and 1980s. This pilot study has shown that the neutron activation analysis technique can determine differences in bone aluminum between McIntyre Powder exposed and non-exposed populations even though 40 years have passed since exposure ceased. The technique has potential application as a biomarker of exposure in cross-sectional studies of the health consequences of exposure to McIntyre Powder.

9.
J Mech Behav Biomed Mater ; 129: 105147, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35290852

RESUMEN

Understanding aging of tooth tissues is the first step to developing robust treatments that support lifelong oral health. In this study selected nanomechanical, compositional and structural parameters of human enamel were characterized to assess the effects of aging on its durability in terms of the apparent fracture toughness (KApp) and brittleness (B). The interdependencies between aging and the enamel properties were assessed using a combination of traditional Pearson's correlation coefficient matrices and self-organizing maps (SOMs) via unsupervised machine learning. To consider age effects, the enamel of three age groups of donor teeth was studied, including primary (donor age ≤10), young (20 age ≤ age ≤50), and old (55 ≤ age) and differences in properties and correlations were identified. Results showed that KApp was negatively correlated to the E, H, degree of crystallinity, and fluoridation, but positively correlated with carbonate content; the opposite trends were observed in B. Interestingly, the SOMs showed that the outer enamel of the old group underwent a degradation in durability (decrease in KApp and increase in B) that was related to multiple contributions, whereas the inner enamel did not undergo this change. Application of K-means clustering on the trained SOMs offered novel insights into the contributions of enamel durability with aging, unique visualization of high-dimensional data onto 2D plots and identified new research directions that would not have otherwise been discovered. Overall, the findings demonstrate the opportunities for understanding aging of enamel using machine learning techniques to pursue age-targeted oral health care.


Asunto(s)
Fracturas de los Dientes , Diente , Envejecimiento , Ciencia de los Datos , Esmalte Dental , Humanos
10.
J Natl Cancer Inst ; 2022 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-35299252

RESUMEN

BACKGROUND: In the US, cancer disproportionately impacts Black and African American individuals. Identifying genetic factors underlying cancer disparities has been an important research focus and requires data that are equitable in both quantity and quality across racial groups. It is widely recognized that DNA databases quantitatively under-represent minorities. However, the differences in data quality between racial groups have not been well studied. METHODS: We compared the qualities of germline and tumor exomes between ancestrally African and European patients in The Cancer Genome Atlas (TCGA) of seven cancers with at least 50 self-reported Black patients in the context of sequencing depth, tumor purity, and qualities of germline variants and somatic mutations. RESULTS: Germline and tumor exomes from ancestrally African patients were sequenced at statistically significantly lower depth in six out of the seven cancers. For three cancers, most ancestrally European exomes were sequenced in early sample batches at higher depth whereas ancestrally African exomes were concentrated in later batches and sequenced at much lower depth. For the other three cancers, the reasons of lower sequencing coverage of ancestrally African exomes remain unknown. Furthermore, even when the sequencing depths were comparable, African exomes had disproportionally higher percentages of positions with insufficient coverage, likely due to the known European bias in the human reference genome that impacted exome capture kit design. CONCLUSIONS: Overall and positional lower sequencing depths of ancestrally African exomes in TCGA led to under-detection and lower quality of variants, highlighting the need to consider epidemiological factors for future genomics studies.

11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(1): 77-82, 2022 Feb 18.
Artículo en Chino | MEDLINE | ID: mdl-35165471

RESUMEN

OBJECTIVE: To evaluate the clinical effect of root canal obturation therapy using cold flowable gutta-percha on young permanent teeth after apexification. METHODS: Ninety cases of young permanent teeth with pulp necrosis or periapical periodontitis treated by apexification were randomly divided into two groups. The cases in each group were divided into single root canal and multiple root canal according to the number of the root canal, and divided into classifications Ⅰ, and Ⅱ/Ⅲ/Ⅳ according to Frank's classification of root development after apexification. Cold flowable gutta-percha and warm gutta-percha obturation techniques were used for root canal obturation of the two groups. The operation time was recorded, and the patients' therapy pain degree was evaluated by visual analog scale (VAS) immediately after operation. Periapical X-ray was performed after operation to evaluate the effect of the root canal filling. The total length of the root was divided into equal three parts on the X-ray film, and three-dimensional tightness of the apical, middle, and coronal region of the root canals were statistically analyzed respectively. Clinical examinations and X-ray examination were performed 6 and 12 months after the operation to evaluate the treatment success rate. RESULTS: The operation time of cold flowable gutta-percha group was significantly lower than that of the control group, which were 51 s and 74 s (P < 0.05); The percentages of pain and discomfort in the two groups were 26.67% and 40.00%, respectively. There were two cases of underfilling and no overfilling in both groups. The percentages of proper filling and tight three-dimensional obturation in the experimental and control groups were 71.11% and 60.00% respectively; and the percentages of tight three-dimensional obturation in the apical third areas were 86.67% and 66.67%, the difference was significant (P < 0.05). There was no significant difference in the three-dimensional tightness between the two groups in the middle and coronal third areas. The percentages of tight three-dimensional obturation in classification Ⅰ groups were 86.67%, 83.33%, 93.33% and 76.67%, 90.00%, 96.67% in experimental and control group, respectively; The percentages of classification Ⅱ/Ⅲ/Ⅳ groups were 86.67%, 86.67%, 100.00% and 46.67%, 86.67%, 100.00%, respectively, and the difference was significant (P < 0.05). There were no apical lesions that occurred in either group during the one-year review period. CONCLUSION: The application of cold flowable gutta-percha on young permanent teeth root canal obturation after apexification can achieve good obturation effect. The root obturation effect in the apical third area is significantly better than that of warm gutta-percha obturation techniques. Cold flowable gutta-percha can shorten the clinical treatment time and ameliorate the patients' therapy comfort.


Asunto(s)
Gutapercha , Materiales de Obturación del Conducto Radicular , Apexificación , Cavidad Pulpar , Humanos , Radiografía , Obturación del Conducto Radicular , Preparación del Conducto Radicular
12.
Int J Comput Dent ; 0(0): 0, 2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-35072420

RESUMEN

PURPOSE: This study aimed to evaluate the stress distribution patterns, resistance to fracture, and failure modes of endodontically treated molars restored with different cuspal coverage options. MATERIALS AND METHODS: Three-dimensional models of mandibular first molars with six kinds of typical cuspal coverage were generated: T1, mesiobuccal cuspal coverage; T2, coverage of all buccal cusps; T3, mesiolingual cuspal coverage; T4, coverage of all lingual cusps; T5, mesiobuccal and mesiolingual cuspal coverage; and T6, coverage of all cusps. All restorations were fabricated with zirconia-reinforced lithium silicate ceramic. The stress and its distributions under axial and oblique loading were analysed by finite element analysis (FEA). Sixty human mandibular molar samples were randomly allocated into 6 groups (n = 10) to simulate the application of six types of restorations with different cuspal coverage as in the FEA analysis and then subjected to a compressive test. All fractured specimens were subjected to fractography. Data were analysed by one-way ANOVA, Tukey's post hoc test, and Fisher's exact test (α = 0.05). RESULTS: The T2 and T6 groups presented superior stress distribution patterns under both axial and oblique loading compared to the other models. The fracture loads in the T2 (1627 ±358 N) and T6 (1639 ±355 N) groups were significantly higher than those in the other groups (P < 0.05). The T2 and T6 groups exhibited more restorable failure modes. Fractography showed more cracks below the cement-enamel junction in the T3, T4, and T5 groups. CONCLUSIONS: Onlay restoration with whole functional cuspal coverage provided comparable effects to coverage of all cusps in endodontically treated molars, and both methods exhibited a more even stress distribution and fracture resistance and better mechanical performance in high occlusal areas than other types of cuspal coverage.

13.
J Clin Invest ; 132(2)2022 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-34813500

RESUMEN

Vast numbers of differentially expressed genes and perturbed networks have been identified in Alzheimer's disease (AD), however, neither disease nor brain region specificity of these transcriptome alterations has been explored. Using RNA-Seq data from 231 temporal cortex and 224 cerebellum samples from patients with AD and progressive supranuclear palsy (PSP), a tauopathy, we identified a striking correlation in the directionality and magnitude of gene expression changes between these 2 neurodegenerative proteinopathies. Further, the transcriptomic changes in AD and PSP brains ware highly conserved between the temporal and cerebellar cortices, indicating that highly similar transcriptional changes occur in pathologically affected and grossly less affected, albeit functionally connected, areas of the brain. Shared up- or downregulated genes in AD and PSP are enriched in biological pathways. Many of these genes also have concordant protein changes and evidence of epigenetic control. These conserved transcriptomic alterations of 2 distinct proteinopathies in brain regions with and without significant gross neuropathology have broad implications. AD and other neurodegenerative diseases are likely characterized by common disease or compensatory pathways with widespread perturbations in the whole brain. These findings can be leveraged to develop multifaceted therapies and biomarkers that address these common, complex, and ubiquitous molecular alterations in neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Parálisis Supranuclear Progresiva/metabolismo , Transcriptoma , Anciano , Femenino , Humanos , Masculino
15.
Hong Kong Med J ; 28(1): 64-72, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33518531

RESUMEN

Intensive care is expensive, and the numbers of intensive care unit (ICU) beds and trained specialist medical staff able to provide services in Hong Kong are limited. The most recent increase in coronavirus disease 2019 (COVID-19) infections over July to August 2020 resulted in more than 100 new cases per day for a prolonged period. The increased numbers of critically ill patients requiring ICU admission posed a capacity challenge to ICUs across the territory, and it may be reasonably anticipated that should a substantially larger outbreak occur, ICU services will be overwhelmed. Therefore, a transparent and fair prioritisation process for decisions regarding patient ICU admission is urgently required. This triage tool is built on the foundation of the existing guidelines and framework for admission, discharge, and triage that inform routine clinical practice in Hospital Authority ICUs, with the aim of achieving the greatest benefit for the greatest number of patients from the available ICU resources. This COVID-19 Crisis Triage Tool is expected to provide structured guidance to frontline doctors on how to make triage decisions should ICU resources become overwhelmed by patients requiring ICU care, particularly during the current COVID-19 pandemic. The triage tool takes the form of a detailed decision aid algorithm based on a combination of established prognostic scores, and it should increase objectivity and transparency in triage decision making and enhance decision-making consistency between doctors within and across ICUs in Hong Kong. However, it remains an aid rather than a complete substitute for the carefully considered judgement of an experienced intensive care clinician.


Asunto(s)
COVID-19 , Hospitalización , Triaje , Adulto , COVID-19/epidemiología , Brotes de Enfermedades , Hong Kong/epidemiología , Humanos , Unidades de Cuidados Intensivos , Pandemias , SARS-CoV-2 , Triaje/métodos
16.
Brain ; 2021 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-34918030

RESUMEN

Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a complex heterogeneous neurodegenerative disorder for which mechanisms are poorly understood. To explore transcriptional changes underlying FTLD-TDP, we performed RNA-sequencing on 66 genetically unexplained FTLD-TDP patients, 24 FTLD-TDP patients with GRN mutations and 24 control subjects. Using principal component analysis, hierarchical clustering, differential expression, and co-expression network analyses, we showed that GRN mutation carriers and FTLD-TDP-A patients without a known mutation shared a common transcriptional signature that is independent of GRN loss-of-function. After combining both groups, differential expression as compared to the control group and co-expression analyses revealed alteration of processes related to immune response, synaptic transmission, RNA metabolism, angiogenesis and vesicle-mediated transport. Deconvolution of the data highlighted strong cellular alterations that were similar in FTLD-TDP A and GRN mutation carriers with NSF as a potentially important player in both groups. We propose several potentially druggable pathways such as the GABAergic, GDNF and sphingolipid pathways. Our findings underline new disease mechanisms and strongly suggest that affected pathways in GRN mutation carriers extend beyond GRN and contribute to genetically unexplained forms of FTLD-TDP-A.

18.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(5): 903-908, 2021 May 10.
Artículo en Chino | MEDLINE | ID: mdl-34814486

RESUMEN

Objective: To investigate the association of lipoprotein a (Lpa) in early pregnancy with gestational diabetes mellitus (GDM) risk. Methods: A total of 445 pregnant women in 12-14 gestational weeks from "Maternal Key Nutritional Factors and Offspring's Atopic Dermatitis" cohort were included in this study. The demographic characteristics of participants were collected by using questionnaires, and the fasting glucose and lipids levels in early pregnancy were measured. The results of oral glucose tolerance test (OGTT) between 24-28 gestational weeks were recorded. Multivariate logistic regression model was applied to analyze the association of Lpa with GDM by calculating the OR and 95%CI after adjustment for covariates. Results: The incidence number of GDM was 78 (17.5%). The Lpa level in pregnant women with GDM was significantly higher than that in pregnant women without GDM [105.5 (92.0, 122.0) vs. 97.0 (87.0, 109.0) mg/L], P<0.05. Lpa was significantly associated with GDM risk [OR (95%CI) =1.21(1.08-1.36) per 10 mg/L], P<0.05. The association was still significant after adjustment for covariates including age, gestational weeks et al, the adjusted OR was 1.14 (95%CI: 1.01-1.30), P=0.03. Conclusions: The elevation of Lpa in early pregnancy is one of risk factor for GDM. Maintaining normal Lpa level during early pregnancy can benefit early prevention of GDM and offspring health.


Asunto(s)
Diabetes Gestacional , Glucemia , Estudios de Cohortes , Diabetes Gestacional/epidemiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Lipoproteína(a) , Embarazo , Estudios Prospectivos , Factores de Riesgo
20.
J Opt Soc Am A Opt Image Sci Vis ; 38(8): 1224-1231, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34613317

RESUMEN

We propose a novel hybrid method for accurately and efficiently analyzing microcavities and nanoresonators. The method combines the marked spirit of quasinormal mode expansion approaches, e.g., analyticity and physical insight, with the renowned strengths of real-frequency simulations, e.g., accuracy and flexibility. Real- and complex-frequency simulations offer a complementarity between accuracy and computation speed, opening new perspectives for challenging inverse design of nanoresonators.

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