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1.
Med Mycol ; 61(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37985734

RESUMO

Although previous studies on the genotypic diversity and antifungal susceptibility of the Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype isolates being dominant, the information about the CNSC isolates from Chinese HIV-infected patients is limited. In this study, 171 CNSC isolates from HIV-infected patients in the Chongqing region of Southwest China were genotyped using the International Society for Human and Animal Mycology-multilocus sequence typing consensus scheme, and their antifungal drug susceptibilities were determined following CLSI M27-A3 guidelines. Among 171 isolates, six sequence types (STs) were identified, including the dominant ST5 isolates, the newly reported ST15, and four diploid VNIII isolates (ST632/ST636). Moreover, a total of 1019 CNSC isolates with STs and HIV-status information were collected and analyzed from Mainland China in the present study. A minimum spanning analysis grouped these 1019 isolates into three main subgroups, which were dominated by the ST5 clonal complex (CC5), followed by the ST31 clonal complex (CC31) and ST93 clonal complex (CC93). The trend of resistance or decreasing susceptibility of clinical CNSC isolates to azole agents within HIV-infected patients from the Chongqing region is increasing, especially resistance to fluconazole.


In this paper, novel ST15 and four diploid VNIII isolates (ST632/ST636) were found in 171 CNSC isolates in Southwest China, including evidence for resistance to fluconazole. Moreover, we clustered the 1019 clinical CNSC isolates reported so far from Mainland China into three major subgroups.


Assuntos
Criptococose , Cryptococcus neoformans , Infecções por HIV , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Criptococose/microbiologia , Criptococose/veterinária , Diploide , Testes de Sensibilidade Microbiana/veterinária , Genótipo , China/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/veterinária
2.
Biomater Res ; 27(1): 78, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563666

RESUMO

Small extracellular vesicles (sEVs) have been identified as a noteworthy paracrine mechanism of intercellular communication in diagnosing and managing neurological disorders. Current research suggests that sEVs play a pivotal role in the pathological progression of pain, emphasizing their critical function in the pathological progression of pain in acute and chronic pain models. By facilitating the transfer of diverse molecules, such as proteins, nucleic acids, and metabolites, sEVs can modulate pain signaling transmission in both the central and peripheral nervous systems. Furthermore, the unique molecules conveyed by sEVs in pain disorders indicate their potential as diagnostic biomarkers. The application of sEVs derived from mesenchymal stem cells (MSCs) in regenerative pain medicine has emerged as a promising strategy for pain management. Moreover, modified sEVs have garnered considerable attention in the investigation of pathological processes and therapeutic interventions. This review presents a comprehensive overview of the current knowledge regarding the involvement of sEVs in pain pathogenesis and treatment. Nevertheless, additional research is imperative to facilitate their clinical implementation. Schematic diagram of sEVs in the biogenesis, signal transmission, diagnosis, and treatment of pain disorders. Small extracellular vesicles (sEVs) are secreted by multiple cells, loading with various biomolecules, such as miRNAs, transmembrane proteins, and amino acids. They selectively target other cells and regulating pain signal transmission. The composition of sEVs can serve as valuable biomarkers for pain diagnosis. In particular, mesenchymal stem cell-derived sEVs have shown promise as regenerative medicine for managing multiple pain disorders. Furthermore, by modifying the structure or contents of sEVs, they could potentially be used as a potent analgesic method.

3.
J Agric Food Chem ; 71(31): 11806-11833, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37467345

RESUMO

In response to the issues of foodborne microbial contamination and carbon neutrality goals, sustainable antimicrobial food packaging (SAFP) composed of renewable or biodegradable biopolymer matrices with ecofriendly antimicrobial agents has emerged. SAFP offers longer effectiveness, wider coverage, more controllability, and better environmental performance. Analyzing SAFP information, including the release profile of each antimicrobial agent for each food, the interaction of each biomass matrix with each food, the material size, form, and preparation methods, and its service quality in real foods, is crucial. While encouraging reports exist, a comprehensive review summarizing these developments is lacking. Therefore, this review critically examines recent release-antimicrobial mechanisms, kinetics models, preparation methods, and key regulatory parameters for SAFPs based on slow- or controlled-release theory. Furthermore, it discusses fundamental physicochemical characteristics, effective concentrations, advantages, release approaches, and antimicrobial and preservative effects of various materials in food simulants or actual food. Lastly, inadequacies and future trends are explored, providing practical references to regulate the movement of active substances in different media, reduce the reliance on petrochemical-based materials, and advance food packaging and preservation technologies.


Assuntos
Anti-Infecciosos , Embalagem de Alimentos , Embalagem de Alimentos/métodos , Conservação de Alimentos/métodos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Biopolímeros
4.
ISA Trans ; 136: 605-621, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36517265

RESUMO

Traditional linear active disturbance rejection control (LADRC) may have difficulty to achieve a rapid precise disturbance rejection for a permanent magnet synchronous linear motor (PMSLM). By making use of model information, a model predictive and compensated LADRC (MPLADRC) method is proposed in this paper. In this method, a model compensated extended state observer (MESO) is designed to transform the controlled object into an established mathematical model through total disturbance compensation. Meanwhile, considering the delay problem of MESO, a phase advance module is designed to improve the estimation speed of MESO for system disturbance and state, thus the MESO can rapidly compensate various uncertainty disturbances to the controlled object in real time. The model predictive controller (MPC) is then designed based on the mathematical model, and its optimal control law is then obtained through a quadratic objective function to further suppress the disturbance unobserved by the designed MESO. The proposed method can thus realize a dual-degree-of-freedom disturbance rejection through the MESO and MPC. The simulation and experimental results validate the effectiveness of the proposed MPLADRC in rapid anti-disturbance and fast positioning for the motion control of the PMSLM.

5.
Int Immunopharmacol ; 111: 109165, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35987144

RESUMO

Severe acute pancreatitis (SAP) is a condition characterized by highly fatal acute inflammation and is usually associated with multiple organ dysfunction syndrome. Acute lung injury (ALI) is the most common complications of SAP, which is the accelerator of other organ dysfunction caused by SAP and the primary cause of early death due to SAP. Acadesine, an adenosine analog and an AMPK activator, has been discovered to modulate glucose and lipid metabolism, and inhibit the production of pro-inflammatory cytokines and iNOS. However, its role in SAP-ALI and its mechanism remains unclear and need to be explored. Herein, we discovered that acadesine mitigated the generation of reactive oxygen species (ROS) in human pulmonary microvascular endothelial cells (HPMECs), alleviated apoptosis and recovered barrier integrity, thereby contributing to anti-inflammatory effects in vitro and in vivo. Moreover, Nrf2 deficiency partially eliminated the effects of acadesine-induced antioxidant effects and thus weakened the protective effects on cells and Nrf2-knockout (Nrf2-/-) mice. This study demonstrates that acadesine attenuated SAP-ALI associated inflammation and tissue damage by modulating the Nrf2-dependent antioxidant pathway by triggering AMPK. These findings are of great significance for the treatment of SAP-related lung injury.


Assuntos
Lesão Pulmonar Aguda , Pancreatite , Proteínas Quinases Ativadas por AMP/metabolismo , Doença Aguda , Lesão Pulmonar Aguda/induzido quimicamente , Aminoimidazol Carboxamida/análogos & derivados , Animais , Antioxidantes/farmacologia , Células Endoteliais/metabolismo , Humanos , Inflamação/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Pancreatite/complicações , Ribonucleosídeos , Transdução de Sinais
6.
Nat Commun ; 13(1): 4852, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982059

RESUMO

To better understand DNA methylation in Alzheimer's disease (AD) from both mechanistic and biomarker perspectives, we performed an epigenome-wide meta-analysis of blood DNA methylation in two large independent blood-based studies in AD, the ADNI and AIBL studies, and identified 5 CpGs, mapped to the SPIDR, CDH6 genes, and intergenic regions, that are significantly associated with AD diagnosis. A cross-tissue analysis that combined these blood DNA methylation datasets with four brain methylation datasets prioritized 97 CpGs and 10 genomic regions that are significantly associated with both AD neuropathology and AD diagnosis. An out-of-sample validation using the AddNeuroMed dataset showed the best performing logistic regression model includes age, sex, immune cell type proportions, and methylation risk score based on prioritized CpGs in cross-tissue analysis (AUC = 0.696, 95% CI: 0.616 - 0.770, P-value = 2.78 × 10-5). Our study offers new insights into epigenetics in AD and provides a valuable resource for future AD biomarker discovery.


Assuntos
Doença de Alzheimer , Epigenoma , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Encéfalo/patologia , Metilação de DNA/genética , Epigênese Genética , Estudo de Associação Genômica Ampla , Humanos
7.
Opt Lett ; 47(14): 3483-3486, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838715

RESUMO

Current binary defocus technology mainly focuses on fringe generation suitable for specific frequencies without considering fringe adaptability for defocus-degree variation, which decreases the measuring accuracy for this scenario. To achieve a high-quality measurement, we propose a robust binary fringe generation method to minimize the phase error caused by changes in defocus and the random error in measurement. In the method, we establish a complete phase error model and construct a novel objective function, to the best of our knowledge, to optimize the binarization threshold of each pixel. Through derivation of the threshold gradient calculation formula, we quickly obtain optimal binary fringes that can adapt to different fringe pitches and various degrees of defocus. The experimental results verify that the proposed method can generate robust binary fringes adaptive to different fringe pitches and defocus degree variation, and thus achieve high-quality 3D measurements.

8.
Immunol Lett ; 241: 23-34, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34740720

RESUMO

Emerging evidence has demonstrated that several microvesicles (MVs) are secreted in bronchoalveolar lavage fluid (BALF) during the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the impact of alveolar macrophage (AM)-derived MVs on epithelial cells and their in vivo effects on ALI/ARDS require further exploration. In this study, MVs were isolated from BALF of mice or mouse alveolar macrophage (MHS) cells by sequential centrifugation and then delivered to epithelial cells or mice. Enzyme-linked immunosorbent assay revealed that BALF-derived MVs (BALF-MVs) and MHS-derived MVs (AM-MVs) were rich in tumor necrosis factor-α (TNF-α) at the early stage of lung injury. In vitro, both inflammatory BALF-MVs and AM-MVs decreased the expression of α subunit of epithelial sodium channel (α-ENaC), γ-ENaC, and Na+,K+-ATPase α1 and ß1 in lung epithelial cells. However, antibodies against TNF-α inhibited the effects of inflammatory AM-MVs in epithelial cells. In vivo, the inflammatory AM-MVs, delivered intratracheally to mice, impaired lung tissues and increased the injury score. They also resulted in decreased alveolar fluid clearance and increased lung wet weight/dry weight ratio. Furthermore, inflammatory AM-MVs downregulated the α-ENaC, γ-ENaC, and Na+,K+-ATPase α1 and ß1 levels in lung tissues. According to our results, inflammatory AM-derived MVs may potentially contribute to lung injury and pulmonary edema, thereby indicating a potential novel therapeutic approach against ALI/ARDS based on AM-MVs.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Células Epiteliais/imunologia , Inflamação/imunologia , Pulmão/patologia , Macrófagos Alveolares/imunologia , Edema Pulmonar/imunologia , Síndrome do Desconforto Respiratório/imunologia , Animais , Células Cultivadas , Canais Epiteliais de Sódio/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , ATPase Trocadora de Sódio-Potássio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Ann Epidemiol ; 64: 53-66, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34438024

RESUMO

PURPOSE: Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health. METHODS: We pooled data from the Mexican Health and Aging Study (N = 17,771) and Mexican-born U.S. Health and Retirement Study (N = 898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration. RESULTS: Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95% CI: 0.89, 1.08]) and women (ratio of average symptom-count = 1.00 [95% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood. CONCLUSIONS: In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms.


Assuntos
Envelhecimento , Depressão , Adulto , Depressão/epidemiologia , Feminino , Humanos , Masculino , México/epidemiologia , Modelos Estatísticos , Aposentadoria
10.
Opt Lett ; 46(15): 3749-3752, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34329272

RESUMO

The measurement accuracy of high-speed binary defocusing fringe projection profilometry depends on the fringe pitch and defocus degree. During the measurement process, the degree of defocus changes with the measurement depth of the scenes. This makes it difficult to obtain a suitable defocus degree and achieve high-precision measurement owing to dynamic changes in the measurement object or environment. To address this problem, we propose a highly dynamic defocus response method to adaptively adjust fringe pitches for binary defocusing fringe projection profilometry. As the defocus degree changes significantly, the proposed method can respond quickly and adjust the fringe pitches adaptively to the scenes. Therefore, a high-precision dynamic measurement can be achieved for the current measuring scene. In this study, considering the effect of random error and nonlinear error, we established a complete phase-error model and used it as an optimization function. Based on this function, we obtained the optimal fringe pitch expression with the defocus degree and harmonic response parameters as variables. With the proposed method, we can obtain the defocus degree and harmonic response parameters during the measurement process and calculate the optimal fringe pitches for the current scenes. Thus, the proposed method can dynamically adapt to the measuring depth change and achieve an accurate measurement without modifying any hardware parameters.

11.
Acta Neuropathol Commun ; 9(1): 77, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902726

RESUMO

Sex is an important factor that contributes to the clinical and biological heterogeneities in Alzheimer's disease (AD), but the regulatory mechanisms underlying sex disparity in AD are still not well understood. DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD. We performed the first large-scale sex-specific meta-analysis of DNA methylation differences in AD neuropathology, by re-analyzing four recent epigenome-wide association studies totaling more than 1000 postmortem prefrontal cortex brain samples using a uniform analytical pipeline. For each cohort, we employed two complementary analytical strategies, a sex-stratified analysis that examined methylation-Braak stage associations in male and female samples separately, and a sex-by-Braak stage interaction analysis that compared the magnitude of these associations between different sexes. Our analysis uncovered 14 novel CpGs, mapped to genes such as TMEM39A and TNXB that are associated with the AD Braak stage in a sex-specific manner. TMEM39A is known to be involved in inflammation, dysregulated type I interferon responses, and other immune processes. TNXB encodes tenascin proteins, which are extracellular matrix glycoproteins demonstrated to modulate synaptic plasticity in the brain. Moreover, for many previously implicated genes in AD neuropathology, such as MBP and AZU1, our analysis provided the new insights that they were predominately driven by effects in only one sex. These sex-specific DNA methylation differences were enriched in divergent biological processes such as integrin activation in females and complement activation in males. Our study implicated multiple new loci and biological processes that affected AD neuropathology in a sex-specific manner.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Metilação de DNA/fisiologia , Bases de Dados Genéticas , Caracteres Sexuais , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia
12.
Epidemiology ; 32(1): 50-60, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33009250

RESUMO

BACKGROUND: Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health. METHODS: We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW. RESULTS: Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models. CONCLUSIONS: Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.


Assuntos
Emigração e Imigração , Migrantes , Envelhecimento , Feminino , Humanos , Recém-Nascido , Masculino , México/epidemiologia , Estados Unidos/epidemiologia
13.
Nat Commun ; 11(1): 6114, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257653

RESUMO

DNA methylation differences in Alzheimer's disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent methylation differences in multiple cohorts. Using a uniform analysis pipeline, we identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our analysis identified differentially methylated genes such as MAMSTR, AGAP2, and AZU1. The most significant DMR identified is located on the MAMSTR gene, which encodes a cofactor that stimulates MEF2C. Notably, MEF2C cooperates with another transcription factor, PU.1, a central hub in the AD gene network. Our enrichment analysis highlighted the potential roles of the immune system and polycomb repressive complex 2 in pathological AD. These results may help facilitate future mechanistic and biomarker discovery studies in AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Metilação de DNA/fisiologia , Epigênese Genética/genética , Imunidade/genética , Córtex Pré-Frontal/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/imunologia , Encéfalo , Proteínas de Transporte/genética , Epigênese Genética/fisiologia , Feminino , Proteínas de Ligação ao GTP/genética , Proteínas Ativadoras de GTPase/genética , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Humanos , Imunidade/fisiologia , Fatores de Transcrição MEF2/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética
14.
BMC Palliat Care ; 19(1): 156, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046031

RESUMO

BACKGROUND: This study aimed to devise a Cancer symptoms Discrimination Scale (CSDS) suitable for China based on a cross-sectional survey. METHODS: The CSDS was developed using the classical measurement theory. A total of 3610 students from Yunnan province, China, participated in the cross-sectional survey. The test version of the scale was modified by the item analysis method, and after the official version of CSDS was developed, its reliability and validity were verified. A univariate analysis of variance and a multiple linear regression model were used to analyze the influencing factors of cancer symptoms discrimination among the university/college students. RESULTS: There were 21 items in total for the CSDS, including 3 subscales --- common clinical manifestations (11 items), physical appearance defects (6 items), and drainage tube(s) wearing (4 items). This CSDS had good validity (GFI = 0.930, AGFI = 0.905, RMR = 0.013, I-CVIs> 0.80, and the Pearson correlation coefficient was satisfactory.) and reliability (Cronbach's alpha = 0.862, spearman-brown coefficient = 0.875). The multiple linear regression showed that certain factors may affect the students' discrimination level against cancer symptoms (P < 0.05), including gender, major, current education degree, guardian's highest record of formal schooling, self-rated health status, history of care for cancer patients, family relationship, ways of cancer knowledge acquisition, good/poor understanding of cancer-related information, degree of cancer fear, and their perception of cancer infectiousness. CONCLUSION: This CSDS, with good reliability and validity, can be used for the evaluation of the discrimination risk and levels against cancer symptoms among healthy students.


Assuntos
Neoplasias/psicologia , Preconceito/psicologia , Discriminação Social/psicologia , Estudantes/psicologia , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Neoplasias/epidemiologia , Reprodutibilidade dos Testes , Estudantes de Ciências da Saúde/psicologia , Inquéritos e Questionários , Universidades , Adulto Jovem
16.
Kidney Int ; 98(1): 187-194, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32471640

RESUMO

The association between dietary sodium and potassium intake with the development of kidney disease remains unclear, particularly among younger individuals. Here, we determined whether dietary sodium and potassium intake are associated with incident chronic kidney disease (CKD) using data from 1,030 adults (age 23-35 in 1990-1991) from the Coronary Artery Risk Development In Young Adults study, based on repeated measurements of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (ACR) from 1995 through 2015. Urinary sodium and potassium excretion (mg/day), calculated from three 24-hour urine collections in 1990-1991, were averaged to measure sodium and potassium intake. Serum creatinine was used to calculate eGFR using the CKD EPI equation; spot urine albumin and creatinine were used to calculate ACR, each at five visits from 1995-1996 through 2015-2016. CKD was defined as decreased eGFR (under 60 ml/min/1.73m2) or the development of albuminuria (ACR over 30 mg/g). We used log binomial regression models adjusted for socio-demographic, behavioral, and clinical factors to determine whether sodium and potassium intake were associated with incident CKD (decreased eGFR or developed albuminuria) among those free of CKD in 1995. Dietary sodium intake was not significantly associated with incident CKD. However, every 1,000 mg/day increment of potassium intake in 1990 was significantly associated with a 29% lower risk of incident albuminuria (relative risk 0.71, 95% confidence interval 0.53, 0.95), but not eGFR. Thus, higher dietary potassium intake may protect against the development of kidney damage, particularly albuminuria.


Assuntos
Potássio na Dieta , Insuficiência Renal Crônica , Adulto , Albuminúria/epidemiologia , Creatinina , Taxa de Filtração Glomerular , Humanos , Rim , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/prevenção & controle , Adulto Jovem
17.
Neurology ; 95(1): e59-e69, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32385188

RESUMO

OBJECTIVE: To identify preferred neurofilament assays and clinically validate serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) as prognostic and potential pharmacodynamic biomarkers relevant to amyotrophic lateral sclerosis (ALS) therapy development. METHODS: In this prospective, multicenter, longitudinal observational study of patients with ALS (n = 229), primary lateral sclerosis (n = 20), and progressive muscular atrophy (n = 11), biological specimens were collected, processed, and stored according to strict standard operating procedures (SOPs). Neurofilament assays were performed in a blinded manner by independent contract research organizations. RESULTS: For serum NfL and pNfH measured using the Simoa assay, there were no missing data (i.e., technical replicates below the lower limit of detection were not encountered). For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ∼4% and ∼10% of serum samples, respectively. Mean coefficients of variation for NfL in serum and CSF were both ∼3%. Mean coefficients of variation for pNfH in serum and CSF were ∼4%-5% and ∼2%-3%, respectively, in all assays. Baseline serum NfL concentration, but not pNfH, predicted the future Revised ALS Functional Rating Scale (ALSFRS-R) slope and survival. Incorporation of baseline serum NfL into mixed effects models of ALSFRS-R slopes yields an estimated sample size saving of ∼8%. Depending on the method used to estimate effect size, use of serum NfL (and perhaps pNfH) as pharmacodynamic biomarkers, instead of the ALSFRS-R slope, yields significantly larger sample size savings. CONCLUSIONS: Serum NfL may be considered a clinically validated prognostic biomarker for ALS. Serum NfL (and perhaps pNfH), quantified using the Simoa assay, has potential utility as a pharmacodynamic biomarker of treatment effect.


Assuntos
Esclerose Lateral Amiotrófica/sangue , Biomarcadores/sangue , Filamentos Intermediários/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Inflamm Bowel Dis ; 26(6): 797-808, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32333601

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage. METHODS: We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples. RESULTS: ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. CONCLUSIONS: The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.


Assuntos
Regulação da Expressão Gênica , Imunossupressores/farmacologia , Síndrome do Intestino Irritável/fisiopatologia , Peptidil Dipeptidase A/genética , Serina Endopeptidases/genética , Adolescente , Adulto , Idoso , Enzima de Conversão de Angiotensina 2 , Animais , Betacoronavirus/metabolismo , Biópsia , COVID-19 , Colo/efeitos dos fármacos , Colo/metabolismo , Biologia Computacional , Infecções por Coronavirus/fisiopatologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Imunossupressores/uso terapêutico , Inflamação/fisiopatologia , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Transcriptoma , Adulto Jovem
19.
Appl Opt ; 59(4): 1082-1091, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32225244

RESUMO

White-light scanning interferometry (WLSI) is an important measurement technique that has been widely used in three-dimensional profile reconstruction. Because of the effects of environmental noise and phase changes caused by surface reflection, existing WLSI algorithms have problems in measurement accuracy and measurement speed. Addressing these problems, this paper proposes a fast template matching method to determine precisely the zero optical path difference (ZOPD) position in the WLSI. Due to the uniform shape of the interference signals, a template interference signal can be obtained in advance by performing a least-square fitting or Fourier interpolation on an interference signal of one pixel. In the method, the ZOPD position is initially obtained by the centroid method. Then, the ZOPD position is determined by a precise matching process through moving the template interference signal on the measured interference signal. Through the two-step processes, the ZOPD position can be obtained precisely with much less time. The method was simulated and verified through the measurement of a spherical surface, a 1.8-µm-height standard step and a flip-chip substrate. The experimental results show that the proposed algorithm can achieve both high precision and fast measurement.

20.
Comput Math Methods Med ; 2019: 4830914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885681

RESUMO

In recent years, we have seen more and more interest in the field of medical images and shape comparison motivated by the latest advances in microcomputed tomography (µCT) acquisition, modelling, and visualization technologies. Usually, biologists need to evaluate the effect of different root canal preparation systems. Current root canal preparation evaluation methods are based on the volume difference, area difference, and transportation of two root canals before and after treatment. The purpose of root canal preparation is to minimize the volume difference and ensure the complete removal of the smear layer. Previous methods can reflect some general geometric differences, but they are not enough to evaluate the quality of root canal shape. To solve this problem, we proposed a novel root canal evaluation method based on spectrum and eigenfunctions of Steklov operators, which can be served as a better alternative to current methods in root canal preparation evaluation. Firstly, the ideal root canal model was simulated according to the root canal model before and after preparation. Secondly, the Steklov spectrum of the two models was calculated. Thirdly, based on the spectrum and the histogram of the Gaussian curvature on the surface, the weight of each eigenvalue was computed. Therefore, the Steklov spectrum distance (SSD), which measures shape difference between the root canals, was defined. Finally, the calculation method that quantifies the root canal preparation effect of root canals was obtained. Through experiments, our method manifested high robustness and accuracy compared with existing state-of-the-art approaches. It also demonstrates the significance of our algorithm's advantages on a variety of challenging root canals through result comparison with counterpart methods.


Assuntos
Cavidade Pulpar/diagnóstico por imagem , Preparo de Canal Radicular/estatística & dados numéricos , Algoritmos , Biologia Computacional , Simulação por Computador , Humanos , Imageamento Tridimensional , Interpretação de Imagem Radiográfica Assistida por Computador , Microtomografia por Raio-X
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