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1.
Am J Hum Genet ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34478634

RESUMO

Haplotype phasing is the estimation of haplotypes from genotype data. We present a fast, accurate, and memory-efficient haplotype phasing method that scales to large-scale SNP array and sequence data. The method uses marker windowing and composite reference haplotypes to reduce memory usage and computation time. It incorporates a progressive phasing algorithm that identifies confidently phased heterozygotes in each iteration and fixes the phase of these heterozygotes in subsequent iterations. For data with many low-frequency variants, such as whole-genome sequence data, the method employs a two-stage phasing algorithm that phases high-frequency markers via progressive phasing in the first stage and phases low-frequency markers via genotype imputation in the second stage. This haplotype phasing method is implemented in the open-source Beagle 5.2 software package. We compare Beagle 5.2 and SHAPEIT 4.2.1 by using expanding subsets of 485,301 UK Biobank samples and 38,387 TOPMed samples. Both methods have very similar accuracy and computation time for UK Biobank SNP array data. However, for TOPMed sequence data, Beagle is more than 20 times faster than SHAPEIT, achieves similar accuracy, and scales to larger sample sizes.

2.
Chem Commun (Camb) ; 57(73): 9178-9191, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519317

RESUMO

Since the discovery of carbocations in 1901, the past 120 years have witnessed many marvelous advances in the chemistry of carbocations. The state-of-the-art research in this field is to overcome the intrinsic instability and high reactivity of the prochiral carbocationic intermediates to develop catalytic asymmetric reactions. Such transformations enable the facile synthesis of structurally diverse value-added products from readily available starting materials such as alkenes, alcohols, and carbonyl derivatives, and enjoy high and even perfect atom-economy in most cases. Notably, such allows catalytic stereoconvergent synthesis from racemic substrates and can realize regioselectivity in olefin functionalization reactions complementary to radical processes. With the rapid developments in modern asymmetric organocatalysis, a variety of highly enantioselective protocols evolving prochiral carbocationic intermediates have been achieved by employing three strategies, namely chiral ion-pairing, chiral nucleophile, or chiral carbenium ion strategy. This feature article aims to summarize the exciting advances in this emerging area and briefly showcase the possible mechanisms. The advantages and limitations of each strategy are presented as well as their synthetic applications in the synthesis of natural products or bioactive compounds.

3.
Food Chem ; 369: 130978, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34500209

RESUMO

In this paper, the effects of soybean protein isolate (SPI) on the formations of five heterocyclic aromatic amines (HAAs) in roasted pork were investigated. The levels of all five HAAs improved upon addition of 2.5% of SPI (P < 0.05). With higher SPI dosage, the levels of HAA decreased after seeing an increase. Two HAAs (MeIQx and 4,8-DiMeIQx) were inhibited by 10.0% of SPI, with the inhibitory efficiencies of 7.0 % and 85.7%, respectively. After being heated, the levels of both the free amino acids and carbonyl groups in the SPI were observed significantly increased, from 55.04 µg g·SPI-1 to 91.66 µg g·SPI-1 and from 123.85 ± 13.07 to 931.78 ± 32.56, respectively (P < 0.05). Therefore, the possible promotion mechanism of the SPI was speculated that the heated SPI would provide both the HAA precursors and carbonyls, which significantly promoted the Strecker degradation and generated more HAA intermediates (P < 0.05).

4.
ACS Nano ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469113

RESUMO

The synergy between metal alloy nanoparticles (NPs) and single atoms (SAs) should maximize the catalytic activity. However, there are no relevant reports on photocatalytic CO2 reduction via utilizing the synergy between SAs and alloy NPs. Herein, we developed a facile photodeposition method to coload the Cu SAs and Au-Cu alloy NPs on TiO2 for the photocatalytic synthesis of solar fuels with CO2 and H2O. The optimized photocatalyst achieved record-high performance with formation rates of 3578.9 for CH4 and 369.8 µmol g-1 h-1 for C2H4, making it significantly more realistic to implement sunlight-driven synthesis of value-added solar fuels. The combined in situ FT-IR spectra and DFT calculations revealed the molecular mechanisms of photocatalytic CO2 reduction and C-C coupling to form C2H4. We proposed that the synergistic function of Cu SAs and Au-Cu alloy NPs could enhance the adsorption activation of CO2 and H2O and lower the overall activation energy barrier (including the rate-determining step) for the CH4 and C2H4 formation. These factors all enable highly efficient and stable production of solar fuels of CH4 and C2H4. The concept of synergistic SAs and metal alloys cocatalysts can be extended to other systems, thus contributing to the development of more effective cocatalysts.

5.
J Adv Nurs ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468043

RESUMO

AIMS: To examine the distributed characteristics and explore the research themes of Doctor of Nursing Practice (DNP) dissertations during the past two decades. DESIGN: A descriptive statistical and visualization bibliometric analysis was conducted. METHODS: Doctor of Nursing Practice dissertations submitted between January 2005 and June 2021 were collected from the ProQuest Dissertations and Theses database. A descriptive statistical analysis was conducted to calculate the distribution of the DNP dissertations by granting institution and the published year of publications. The VOSviewer 1.6.13 was used to explore the bibliometric networks and research priorities of the DNP dissertations. RESULTS: A total of 4989 DNP dissertations from 90 universities were included in this study, all from the United States. The number of DNP dissertations showed an upward trend, with steady growth from 2005 to 2014 and rapid growth after 2015. The DNP studies focused on five areas: health care management in clinical nursing, advanced practice in nursing education and health education, public health problems, mental health care for adolescents and nurses and the older people care and long-term care. CONCLUSION: Parallel to the numerical increase in DNP dissertations is a steady expansion in the range of research topics and scopes, which is aligned with specific specializations of the DNP. Many are interdisciplinary and employ techniques imported from the fields of public health, psychology and social sciences, resulting in nursing educators and practitioners continually broaden their subject perspectives. IMPACT: Knowing where, when and why DNP research trends developed will help nursing educators to further develop DNP education and optimize DNP programs in the future, such as paying more attention to the nursing practice. Moreover, this study will inspire DNP students and researchers to expand their subject perspectives and broaden the research scope to solve nursing practice problems based on interdisciplinary theories and methods.

6.
BMJ Open ; 11(9): e051172, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475185

RESUMO

OBJECTIVES: The sensitivity of ECG for detecting left ventricular hypertrophy (LVH) is low. The aim of this study was to explore a better ECG criterion for screening LVH in a large general Chinese population. DESIGN: Case-control study. SETTING: China Medical University in Shenyang, China. PARTICIPANTS: All permanent residents in Dawa, Zhangwu and Liaoyang aged 35 years or older were invited. Participants with unqualified data, pacemaker rhythm, frequent premature ventricular beats, Wolff-Parkinson-White syndrome, complete bundle branch block, myocardial infarction or hypertrophic cardiomyopathy were excluded. A total of 10 360 subjects (4630 males) were recruited. INTERVENTIONS: A novel ECG criterion (Northeast China Rural Cardiovascular Health Study (NCRCHS)) composed of different ratios of maximum R wave in lead V5 or V6 (RV5/V6), S wave in lead V3 (SV3) and R wave in lead aVL (RaVL) was proposed and validated using multiple linear regression. Receiver-operating characteristic curves were used to compare the NCRCHS criterion with traditional criteria for LVH detection. RESULTS: An optimised model (15*RaVL+8*SV3+7*RV5/V6) was constructed (R2 0.192, p<0.001) with the cut-off values of 36.8 mV for males and 26.1 mV for females. The maximum area under the curve was obtained using the NCRCHS criterion (male 0.74, 95% CI 0.73 to 0.75; female 0.73, 95% CI 0.72 to 0.75), followed by Cornell voltage criterion, Sokolow-Lyon criterion, Peguero-Lo Presti criterion, multi-ethnic study of atherosclerosis (MESA)-specific criterion and Syst-Eur voltage criterion. Compared with the Cornell voltage criterion, the NCRCHS criterion had a significantly higher sensitivity for detecting LVH at the same level of specificity (p<0.05). CONCLUSIONS: The NCRCHS criterion significantly improved sensitivity for LVH detection in a general Chinese population, with cut-off values of 36.8 and 26.1 mV for males and females, respectively. This criterion can detect LVH earlier and better and may prevent subsequent cardiovascular diseases.


Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Bloqueio de Ramo , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Eletrocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Masculino
7.
Toxicology ; 461: 152923, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474091

RESUMO

Receptor-interacting protein kinase (RIPK) 3-dependent necroptosis plays a critical role in alcoholic liver disease. RIPK3 also facilitates steatosis, oxidative stress, and inflammation. Pterostilbene (PTS) has favorable hepatoprotective activities. The present study was aimed to reveal the therapeutic effects of PTS on ethanol-induced hepatocyte necroptosis and further illustrate possible molecular mechanisms. Human hepatocytes LO2 were incubated with 100 mM ethanol for 24 h to mimic alcoholic hepatocyte injury. Results showed that PTS at 20 µM reduced damage-associated molecular patterns (DAMPs) release, including IL-1α and high-mobility group box 1 (HMGB1), and blocked necroptotic signaling, evidenced by decreased RIPK1 and RIPK3 expression. Trypan blue staining visually showed that PTS reduced nonviable hepatocytes after ethanol exposure, which was counteracted by adenovirus-mediated ectopic overexpression of RIPK3 but not RIPK1. Besides, PTS inhibited ethanol-induced hepatocyte steatosis via restricting lipogenesis and enhancing lipolysis, decreased oxidative stress via rescuing mitochondrial membrane potential, reducing oxidative system, and enhancing antioxidant system, and relieved inflammation evidenced by decreased expression of proinflammatory factors. Notably, RIPK3 overexpression diminished these protective effects of PTS. Subsequent work indicated that PTS suppressed the expression and nuclear translocation of nuclear factor of activated T-cells 4 (NFATc4), an acetylated protein, in ethanol-exposed hepatocytes, while NFATc4 overexpression impaired the negative regulation of PTS on RIPK3 and DAMPs release. Further, PTS rescued sirtuin 2 (SIRT2) expression, and SIRT2 knockdown abrogated the inhibitory effects of PTS on nuclear translocation and acetylation status of NFATc4 in ethanol-incubated hepatocytes. In conclusion, PTS attenuated RIPK3-dependent hepatocyte necroptosis after ethanol exposure via SIRT2-mediated NFATc4 deacetylation.

8.
J Exp Clin Cancer Res ; 40(1): 290, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526098

RESUMO

BACKGROUND: Accumulating evidence indicates that circRNAs may serve as essential regulators in the progression of several human cancers, but the function and mechanism of circRNAs in intrahepatic cholangiocarcinoma (ICC) are largely unknown. METHODS: RNA-seq was used to assess differentially expressed circRNAs between 4 ICC and peritumor tissues. Quantitative RT-PCR and in situ hybridization were used to determine the circHMGCS1-016 expression in ICC tissues. The function and mechanism of circHMGCS1-016 were further identified via in vivo experiments. The clinical characteristics and prognostic significance of circHMGCS1-016 were analyzed by a retrospective study. The functions of circHMGCS1-016 were assessed via modifying circRNA expression in ICC cells. Moreover, the molecular mechanisms of circHMGCS1-016 in ICC cells were explored by circRNA precipitation, miRNA immunoprecipitation, SILAC and luciferase reporter assays. RESULTS: We identified that compared with peritumor tissues, ICC tissues expressed hsa_circ_0008621 (circHMGCS1-016) high by RNA-seq, which was further identified by qRT-PCR and in situ hybridization. Moreover, the expression of circHMGCS1-016 was revealed to be associated with survival and recurrence of ICC patients. By regulating circHMGCS1-016 expression, we found that elevated circHMGCS1-016 promoted ICC development both in vitro and in vivo. By SILAC and circRNA-pull down, we demonstrated that circHMGCS1-016 induced ICC cell invasion and reshaped the tumor immune microenvironment via the miR-1236-3p/CD73 and GAL-8 axis. In ICC tissues, we uncovered that a high level of circHMGCS1-016 was positively associated with CD73 and GAL-8 expression and negatively related to the CD8+ T cells infiltration, which was further validated by establishing a humanized mouse tumor model. Importantly, we displayed that ICC patients with high levels of circHMGCS1-016 in tumor tissues benefited less from anti-PD1 treatment compared to those with low levels of circHMGCS1-016. CONCLUSIONS: CircHMGCS1-016 is a forceful contributor in ICC development and immune tolerance via miR-1236-3p/CD73 and GAL-8 axis. CircHMGCS1-016 can be explored as a new potential biomarker and therapeutic target for PD1-resistant ICC.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34543000

RESUMO

Immunotherapy is currently an important adjuvant therapy for malignant tumors besides surgical treatment. However, the heterogeneity and low immunogenicity of the tumor are two main challenges of the immunotherapy. Here, we have constructed a nanoplatform (CP@mRBC-PpIX) to realize reversion of the tumor acidosis and hypoxia through alkali and oxygen generation triggered by tumor acidosis. By targeting tumor universal features other than endogenous biomarkers, it was found that CP@mRBC-PpIX could polarize tumor-associated macrophages to anti-tumor M1 phenotype macrophages to enhance tumor immune response. Furthermore, under regional light irradiation, the reactive oxygen species produced by photosensitizers located in CP@mRBC-PpIX could increase the immunogenicity of tumors, so that tumor changes from an immunosuppressive "cold tumor" to an immunogenic "hot tumor," thereby increasing the infiltration and response of T cells, further amplifying the effect of immunotherapy. This strategy circumvented the problem of tumor heterogeneity to realize a kind of broad-spectrum immunotherapy, which could effectively prevent tumor metastasis and recurrence.

10.
J Pathol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34543445

RESUMO

Lynch Syndrome (LS) confers inherited cancer predisposition due to germline mutations in a DNA mismatch repair (MMR) gene, e.g. MSH2. MMR is a repair pathway for removal of base mismatches and insertion/deletion loops caused by endogenous and exogenous factors. Loss of MMR through somatic alteration of the wild-type allele in LS results in defective MMR (dMMR). Lifestyle/environmental factors can modify colorectal cancer risk in sporadic and LS patients. Ethanol and its metabolite acetaldehyde are classified as group one carcinogens, and acetaldehyde causes a range of DNA lesions. However, DNA repair pathways responsible for correcting most of such DNA lesions remain uncharacterised. We hypothesised that MMR plays a role in protecting colorectal epithelium from ethanol/acetaldehyde-induced DNA damage. Here, an LS mouse model (intestinal epithelial conditional-knockout for Msh2) was used to determine if there is a gene/environment interaction between dMMR and ethanol/acetaldehyde that accelerates colorectal tumourigenesis in LS. Mice underwent either long-term ethanol-treatment or water-treatment. Most ethanol-treated mice demonstrated colonic hyperproliferation and adenoma formation (with some invasive adenocarcinomas) within 6 months (15/23, 65%), compared with one colonic tumour after 15 months in water-treated mice (1/23, 4%) (p<0.0001, Fisher's exact test). A significantly greater number of dMMR colonic crypt foci precursors were observed in ethanol-treated compared with water-treated mice (p=0.0029, Student's t-test). Moreover, increased plasma acetaldehyde levels were detected in ethanol-treated compared with water-treated mice (p=0.0019, Mann-Whitney U-test), along with significantly increased DNA damage response in the colonic epithelium. Long-term ethanol treatment was associated with significantly increased colonic epithelial proliferation and markedly reduced apoptosis in dMMR adenomas, consistent with enhanced survival of aberrant dMMR relative to MMR-proficient colonic epithelium. In conclusion, there is strong evidence for a gene/environment interaction between dMMR/acetaldehyde, causing acceleration of dMMR-driven colonic tumour formation in this LS model, indicating that advice to limit alcohol consumption should be considered for LS patients. This article is protected by copyright. All rights reserved.

11.
J Agric Food Chem ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544239

RESUMO

Herbivore-induced plant volatiles (HIPVs) play an important role in insect resistance. As a common HIPV in tea plants (Camellia sinensis), ß-ocimene has shown anti-insect function in other plants. However, whether ß-ocimene in tea plants also provides insect resistance, and its mechanism of synthesis and emission are unknown. In this study, ß-ocimene was confirmed to interfere with tea geometrid growth via signaling. Light was identified as the key factor controlling regular emission of ß-ocimene induced by the wounding from tea geometrids. ß-Ocimene synthase (CsBOS1) was located in plastids and catalyzed ß-ocimene formation in overexpressed tobacco. CsBOS1 expression in tea leaves attacked by tea geometrids showed a day-low and night-high variation pattern, while CsABCG expression involved in volatile emission showed the opposite pattern. These two genes might regulate the regular ß-ocimene emission from tea plants induced by tea geometrid attack. This study advances the understanding on HIPV emission and signaling in tea plants.

12.
Toxicol Appl Pharmacol ; : 115725, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536444

RESUMO

An effective in vitro screening assay to detect seizure liability in preclinical development can contribute to better lead molecule optimization prior to candidate selection, providing higher throughput and overcoming potential brain exposure limitations in animal studies. This study explored effects of 26 positive and 14 negative reference pharmacological agents acting through different mechanisms, including 18 reference agents acting on glutamate signaling pathways, in a brain slice assay (BSA) of adult rat to define the assay's sensitivity, specificity, and limitations. Evoked population spikes (PS) were recorded from CA1 pyramidal neurons of hippocampus (HPC) in the BSA. Endpoints for analysis were PS area and PS number. Most positive references (24/26) elicited a concentration-dependent increase in PS area and/or PS number. The negative references (14/14) had little effect on the PS. Moreover, we studied the effects of 15 reference agents testing positive in the BSA on spontaneous activity in E18 rat HPC neurons monitored with microelectrode arrays (MEA), and compared these effects to the BSA results. From these in vitro studies we conclude that the BSA provides 93% sensitivity and 100% specificity in prediction of drug induced seizure liability, including detecting seizurogenicity- by 3 groups of metabotropic glutamate receptor (mGluR) ligands. The MEA results seemed more variable, both quantitatively and directionally, particularly for endpoints capturing synchronized electrical activity. We discuss these results from the two models, comparing each with published results, and provide potential explanations for differences and future directions.

13.
Eur J Prev Cardiol ; 28(11): 1250-1258, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34551085

RESUMO

BACKGROUND: Recent studies have investigated the association of transitions in metabolic health and obesity status over time with the risk of cardiovascular disease, focusing on the subgroup demonstrating metabolically healthy obesity. However, these studies have produced inconsistent results. This study evaluates the relation in a general Chinese population. METHODS: We conducted a prospective cohort study in a general population in Northeast China, with examinations of cardiovascular health from 2012-2015 and follow-up for incident cardiovascular disease until 2018. Cox proportional hazards and logistic regression models were used to investigate the association of baseline metabolic health and obesity status and transitions in those statuses with cardiovascular disease risk. RESULTS: A total of 7472 participants aged ≥35 years who were free of cardiovascular disease at baseline were included in this analysis. Over a median follow-up of 4.66 years, a total of 344 cardiovascular disease events occurred. Among the 3380 participants who were obese at baseline, 37.1% were metabolically healthy. Metabolically healthy obesity was associated with a 48% increased risk of cardiovascular disease (hazard ratio: 1.48; 95% confidence interval: 1.07-2.06) compared with the metabolically healthy non-obese group at baseline. Transition from metabolically healthy obesity to metabolically unhealthy obesity was associated with elevated cardiovascular disease risk with an odds ratio of 1.82 (95% confidence interval: 1.06-3.14) compared with metabolically healthy non-obesity throughout after adjustment. Even maintaining metabolically healthy obesity over time was associated with a higher risk of cardiovascular disease (odds ratio: 1.72; 95% confidence interval: 1.00-2.97). CONCLUSIONS: Weight control and management of existing metabolic disorders should be prioritized in all obese population.

14.
Trials ; 22(1): 530, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380536

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up. METHODS/DESIGN: This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test. DISCUSSION: Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20-35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02936375 . Registered on October 18, 2016.


Assuntos
Azatioprina , Nefrite Lúpica , Azatioprina/efeitos adversos , Cromonas , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Sulfonamidas , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-34333216

RESUMO

The root and rhizome of Sophora tonkinensis Gagnep. (ST) are widely used for the treatment of tonsillitis, sore throats, and heat-evil-induced diseases in traditional Chinese medicine. However, the clinical application of ST is relatively limited due to its toxicity. The mechanism and material basis of ST-induced pulmonary toxicity are still unclear. In the present research, integrated omics and bioinformatics analyses were used to investigate the toxic mechanism and material basis of ST in lung tissue. Proteomics and metabonomics were integrated to analyze the differentially expressed proteins and metabolites. Joint pathway analysis was used to analyze the significantly dysregulated pathways. PubChem and the Comparative Toxicogenomics Database were applied for the screen of toxic targets and compounds. Integrated omics revealed that 323 proteins and 50 metabolites were differentially expressed after treating with ST, out of which 19 proteins and 1 metabolite were significantly enriched in seven pathways. Bioinformatics showed that 15 compounds may indirectly affect the expression of 9 toxic targets of ST. Multiple toxic targets of ST-induced pulmonary injury were found in the study, whose dysregulation may trigger pulmonary cancer, dyspnea, and oxidative stress. Multiple compounds may be the toxic material basis in response to these effects.

16.
Sleep Med ; 85: 246-258, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34388503

RESUMO

OBJECTIVE: The Corona Virus Disease-19 (COVID-19) pandemic has evolved into the largest public health event in the world. Earlier COVID-19 studies have reported that the pandemic caused widespread impacts on mental health and sleep in the general population. However, it remains largely unknown how the prevalence of mental health problems and sleep disturbance developed and interacted in adolescents at different times in the epidemic. METHODS: 831 teenagers (aged 14-19) underwent a longitudinal follow-up study to evaluate the prevalence of mental health problems and sleep disturbance among adolescents before, during, and after the COVID-19 breakout in China and to explore the interaction between mental health and sleep across the three measurements. The chronotype, anxiety and depression level, sleep quality, and insomnia were investigated during each measurement. RESULTS: The adolescents had delayed sleep onset and sleep offset time, longer sleep duration during the quarantine than before and after the epidemic, whereas their chronotype tended to morning type during the epidemic. Yet, the highest prevalence of anxiety, depression, poor sleeper, and insomnia symptoms were observed before but not during the COVID-19 breakout. The females and adolescents who were eveningness type showed significantly higher anxiety and depression levels, poorer sleep quality, and severe insomnia status than the males and the intermediate and morning types. Sleep disturbance was positively associated with mental problems among three measurements. Pre-measured depression level significantly predicted sleep disturbance level at follow-ups. CONCLUSION: These findings suggested that adolescents' high prevalence of mental health and sleep problems occurred before the COVID breakout and decreased during and after the epidemic. Gender and chronotype were significant risk factors associated with affective and sleep disturbances. Depression positively predicted later sleep problems, but not vice versa.


Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Adolescente , Ansiedade/epidemiologia , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Saúde Mental , SARS-CoV-2 , Sono , Distúrbios do Início e da Manutenção do Sono/epidemiologia
17.
Respir Med ; 187: 106564, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391118

RESUMO

OBJECTIVE: To study how demographic differences impact disease manifestation of sarcoidosis using the WASOG tool in a large multicentric study. METHODS: Clinical data regarding 1445 patients with sarcoidosis from 14 clinical sites in 10 countries were prospectively reviewed from Feb 1, 2020 to Sep 30, 2020. Organ involvement was evaluated for the whole group and for subgroups differentiated by sex, race, and age. RESULTS: The median age of the patients at diagnosis was 46 years old; 60.8% of the patients were female. The most commonly involved organ was lung (96%), followed by skin (24%) and eye (22%). Black patients had more multiple organ involvement than White patients (OR = 3.227, 95% CI: 2.243-4.643) and females had more multiple organ involvement than males (OR = 1.238, 95% CI: 1.083-1.415). Black patients had more frequent involvement of neurologic, skin, eye, extra thoracic lymph node, liver and spleen than White and Asian patients. Women were more likely to have eye (OR = 1.522, 95%CI: 1.259-1.838) or skin involvement (OR = 1.369, 95%CI: 1.152-1.628). Men were more likely to have cardiac involvement (OR = 1.326, 95%CI: 1.096-1.605). A total of 262 (18.1%) patients did not receive systemic treatment for sarcoidosis. Therapy was more common in Black patients than in other races. CONCLUSION: The initial presentation and treatment of sarcoidosis was related to sex, race, and age. Black and female individuals are found to have multiple organ involvement more frequently. Age at diagnosis<45, Black patients and multiple organ involvement were independent predictors of treatment.

18.
Talanta ; 234: 122630, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364439

RESUMO

We developed a simple and highly-selective method for 5-methylcytosine detection of specific gene sequence based on binary-probe DNA hybridization. The sequence complementary to the target was designed into two probes, and each fragment of binary probes bound to a relatively short sequence of the target, which made it sensitive to the base mismatches introduced by bisulfite treatment. The advantages of a low detection limit of methylation abundance of 0.1% for the fully methylated target and high sensitivity of 10 pM have been proved by the successful design of binary-probe hybridization. The successful design of the binary probes makes it possible to quantify the average methylation levels of five CpG sites. Thirty-two DNA strands containing 5, 4, 3, 2, 1 and 0 CpG sites were successfully analyzed with the same pair of binary probes. The higher the average methylation level of the target was, the higher the degree of the hybridization reaction. Based on the simple construction of the binary-probe hybridization, the developed biosensor exhibited signals proportional to the average methylation level of the vimentin gene and could evaluate the average methylation level of artificial mixtures. Furthermore, the method has been used to detect vimentin methylation in a genomic context with good specificity, which indicated its potential in the pre-diagnosis of methylation related disease.


Assuntos
Técnicas Biossensoriais , Metilação de DNA , DNA , Sondas de DNA/genética , Hibridização de Ácido Nucleico
19.
Polymers (Basel) ; 13(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34451293

RESUMO

Bone tissue engineering commonly encompasses the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the propagation of cells to regenerate damaged tissues or organs. 3D printing technology has been extensively applied to allow direct 3D scaffolds manufacturing. Polycaprolactone (PCL) has been widely used in the fabrication of 3D scaffolds in the field of bone tissue engineering due to its advantages such as good biocompatibility, slow degradation rate, the less acidic breakdown products in comparison to other polyesters, and the potential for loadbearing applications. PCL can be blended with a variety of polymers and hydrogels to improve its properties or to introduce new PCL-based composites. This paper describes the PCL used in developing state of the art of scaffolds for bone tissue engineering. In this review, we provide an overview of the 3D printing techniques for the fabrication of PCL-based composite scaffolds and recent studies on applications in different clinical situations. For instance, PCL-based composite scaffolds were used as an implant surgical guide in dental treatment. Furthermore, future trend and potential clinical translations will be discussed.

20.
BMC Infect Dis ; 21(1): 834, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412615

RESUMO

BACKGROUND: To verify the efficacy and safety of an inexpensive standardized regimen for multidrug-resistant tuberculosis (MDR-TB) with low resistance to isoniazid (INH), a multicenter prospective study was conducted in eastern China. METHODS: Patients diagnosed as MDR-TB with low concentration INH resistance and rifampicin resistance, second-line/injectable agents sensitive were prospectively enrolled, given the regimen of Amikacin (Ak)-Fluoroquinolones (FQs)-Cycloserine (Cs)-Protionamide (Pto)-PasiniaZid (Pa)-Pyrazinamide (Z) for 6 months followed by 12 months of FQs-Cs-Pto-Pa-Z, and then followed up for treatment outcomes and adverse events (AEs). RESULTS: A total of 114 patients were enrolled into the study. The overall favorable treatment rate was 79.8% (91/114). Among 91 cases with favorable treatment, 75.4% (86/114) were cured and 4.4% (5/114) were completed treatment. Regarding to unfavorable outcomes, among 23 cases, 8.8% (10/114) had failures, 8.8% (10/114) losing follow up, 0.9% (1/114) had treatment terminated due to intolerance to drugs and 1.8% (2/114) died. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78, p 0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients (26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42). CONCLUSIONS: The regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population, especially for newly-treated patients, which could be expected to be developed into a short-course regimen. Clinical trials registration China Clinical Trial Registry ChiCTR-OPC-16009380.

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