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1.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 533-538, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34225427

RESUMO

Objective: To preliminary explore the changes in blood system in pyrrolizidine alkaloids (PAs)-related liver damage. Methods: General situation, liver function, biochemical blood test, routine blood test, coagulation function markers, etc., of 77 cases with drug-induced liver damage admitted to the Zhongshan Hospital Affiliated to Fudan University from 2012 to 2019 were retrospectively analyzed. Patients' were divided into PA group, other traditional Chinese medicine group and Western medicine group according to their medication history. Simultaneously, the changes in liver function were observed in the established mice model of monocrotaline-induced liver damage. Liver tissues HE staining and blood routine indexes were observed. Results: 24 cases received PA, 24 cases received other traditional Chinese medicine, and 29 cases received western medicine. Alanine aminotransferase was lower in PA group than the other two groups (P < 0.05), and the total bilirubin and direct bilirubin were significantly lower than the other traditional Chinese medicine group (P < 0.05). The peripheral platelet count of the PA group was (84.11 ± 26.91) ×10(9)/L, which was significantly lower than the lower limit of normal, and had statistically significant difference with other traditional Chinese medicine and western medicine group (P < 0.01). Thrombocytocrit, mean platelet volume and platelet indices of PA group were statistically different from the other two groups (P < 0.05). The D-dimer level in patients with PA group was (2.62 ± 1.93) mg/L, which was higher than the upper limit of normal, and significantly higher than the D-dimer level of the other two groups of patients (P < 0.01). Meanwhile, prothrombin time was longer in PA group than that of the other two groups (P < 0.01), and platelets count were decreased significantly in the mouse model of monocrotaline-induced liver damage after alanine aminotransferase and aspartate aminotransferase elevation (P < 0.01). Conclusion: PA-related liver damage has lower peripheral platelet counts, and the peripheral platelet counts of these patients are lower than other types of drug-induced liver damage. In addition, increased D-dimer in patients with PA-related liver damage indicate a potential risk of thrombosis.


Assuntos
Alcaloides de Pirrolizidina , Alanina Transaminase , Animais , Aspartato Aminotransferases , Humanos , Fígado , Camundongos , Alcaloides de Pirrolizidina/toxicidade , Estudos Retrospectivos
2.
Mediators Inflamm ; 2021: 9828995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220336

RESUMO

Prenatal opioid exposure might disturb epigenetic programming in the brain of neonatal offspring with various consequences for gene expressions and behaviors. This study determined whether altered trimethylation of histone 3 at lysine 4 (H3K4me3) in the promoter of the tumor necrosis factor-α (tnf-α) gene with neural cell apoptosis was involved in the ventral-medial striatum, an important brain region for withdrawal symptoms, of neonatal rat offspring from morphine-addicted mothers. Female adult rats were injected with morphine before gestation and until 14 days after giving birth. On postnatal day 14 (P14), rat offspring from morphine-addicted mothers were subjected to an opioid-withdrawal protocol and were analyzed 2 or 8 h after administration of that protocol. Expressions of the TNF-α protein, H3K4me3 in the tnf-α promoter gene, and neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring were evaluated. In the absence of significant opioid withdrawal (2 h after initiation of the opioid-withdrawal protocol on P14), prenatal morphine exposure led to increased levels of H3K4me3 in the tnf-α promoter gene, of the TNF-α protein, and of neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring. Following opioid withdrawal (8 h after initiation of the opioid-withdrawal protocol on P14), differential expression of H3K4me3 in the tnf-α promoter gene locus and upregulation of the level of TNF-α protein expression were further enhanced in these offspring. In addition, increased levels of caspase-3 and neural cell apoptosis were also observed. Taken together, this study revealed that prenatal opioid exposure can activate an epigenetic histone mechanism which regulates proinflammatory factor generation, which hence, led to cell apoptotic damage within the ventral-medial striatum of neonatal rat offspring from morphine-addicted mothers. More importantly, the opioid-withdrawal episode may provide augmented effects for the abovementioned alterations and could lead to deleterious effects in the neonatal brain of such offspring.

3.
Science ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34261813

RESUMO

The Crab Nebula is a bright source of gamma-rays powered by the Crab Pulsar's rotational energy, through the formation and termination of a relativistic electron-positron wind. We report the detection of γ-rays from this source with energies from 5 × 10-4 to 1.1 petaelectronvolts (PeV), with a spectrum showing gradual steepening over three energy decades. The ultra-high-energy photons imply the presence of a PeV electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 pc, and magnetic field ≈110 µG. The production rate of PeV electrons, 2.5 × 1036 erg s-1, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of PeV protons to the production of the highest energy γ-rays.

4.
Bull Exp Biol Med ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302204

RESUMO

The study examines the problem whether pyroptosis of U87-MG glioblastoma cells can result from activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) by a local anesthetic. Glioblastoma cells exposed to various concentrations of typical local anesthetic lidocaine demonstrated augmented cytosolic flux of Ca2+, while suppression of CaMKII expression with the corresponding siRNA significantly inhibited this effect in cells treated with 2 mM lidocaine. Lidocaine up-regulated the expression of mRNA caspase-3 and gasdermin GSDME proteins, whereas silencing of CaMKII gene with siRNA significantly moderated this effect. In addition, lidocaine inhibited proliferation of U87-MG cells, and this effect was prevented by silencing CaMKII gene. Thus, lidocaine activated protein kinase CaMKII, which phosphorylated TRPV1 ion channels and induced calcium overload of U87-MG glioblastoma cells, thereby provoking their pyroptosis.

5.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(7): 1050-1055, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34308855

RESUMO

OBJECTIVE: To investigate the association of the number and quality of embryos transferred in frozen-thawed embryo transfer (FET) cycle with the occurrence of early pregnancy loss in infertile women at an advanced age. METHODS: We collected the data of a total of 2622 infertile women aged 36 years or older receiving FET between January, 2015 and December, 2018. The occurrence of early pregnancy loss was analyzed in these women, and the relation of age, the number and quality of embryos transferred with early pregnancy loss was explored in the overall cohort and in different age (36-37, 38-39, 40, 41, 42, 43, 44 and 45-48 years) groups. RESULTS: Of the 2622 women, 976 (37.2%) achieved clinical pregnancy after FET, among whom 241 (24.7%) experienced early pregnancy loss. The clinical pregnancy rate and live birth rate decreased significantly and early pregnancy loss rate increased markedly with age (P < 0.001). The age at both FET and oocyte pick-up was significantly higher in early pregnancy loss group than ongoing pregnancy group. Compared with those with ongoing pregnancy, the women with early pregnancy loss had a significantly greater number of D3 embryos transferred (0.97 vs 0.81) and a lower number of implanted embryos (1.09 vs 1.25). The early pregnancy loss rates was not significantly correlated with the number and quality of embryo transferred across all the age groups. CONCLUSIONS: In infertile women at an advanced age, the early pregnancy loss rate in FET cycle increases with age. An advanced age is an inherent risk factor for early pregnancy loss, therefore ART should be implemented as soon as possible for these women. To reduce early pregnancy loss rate and balance the risk of multiple pregnancies, the number of embryos transferred should be carefully determined on the basis of embryo quality.


Assuntos
Aborto Espontâneo , Infertilidade Feminina , Aborto Espontâneo/epidemiologia , Adulto , Criopreservação , Transferência Embrionária , Feminino , Fertilização In Vitro , Humanos , Infertilidade Feminina/terapia , Gravidez , Taxa de Gravidez , Gravidez Múltipla , Estudos Retrospectivos
6.
Phys Rev Lett ; 126(24): 241103, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34213924

RESUMO

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25 TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17_{stat}±0.02_{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160 TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

7.
Sensors (Basel) ; 21(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207927

RESUMO

The use of heart rate variability (HRV) in research has been greatly popularized over the past decades due to the ease and affordability of HRV collection, coupled with its clinical relevance and significant relationships with psychophysiological constructs and psychopathological disorders. Despite the wide use of electrocardiograms (ECG) in research and advancements in sensor technology, the analytical approach and steps applied to obtain HRV measures can be seen as complex. Thus, this poses a challenge to users who may not have the adequate background knowledge to obtain the HRV indices reliably. To maximize the impact of HRV-related research and its reproducibility, parallel advances in users' understanding of the indices and the standardization of analysis pipelines in its utility will be crucial. This paper addresses this gap and aims to provide an overview of the most up-to-date and commonly used HRV indices, as well as common research areas in which these indices have proven to be very useful, particularly in psychology. In addition, we also provide a step-by-step guide on how to perform HRV analysis using an integrative neurophysiological toolkit, NeuroKit2.


Assuntos
Eletrocardiografia , Psicofisiologia , Frequência Cardíaca , Reprodutibilidade dos Testes
8.
Phys Rev Lett ; 126(25): 252501, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34241497

RESUMO

Direct proton-knockout reactions of ^{55}Sc at ∼220 MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of ^{54}Ca were investigated through γ-ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological internucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the ^{55}Sc ground state with states in ^{54}Ca. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of ^{55}Sc, valence proton removals populated predominantly the ground state of ^{54}Ca. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.

9.
Eur Cell Mater ; 41: 43-62, 2021 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-34275129

RESUMO

Dentineogenesis starts on odontoblasts, which synthesise and secrete non-collagenous proteins (NCPs) and collagen. When dentine is injured, dental pulp progenitors/mesenchymal stem cells (MSCs) can migrate to the injured area, differentiate into odontoblasts and facilitate formation of reactionary dentine. Dental pulp progenitor cell/MSC differentiation is controlled at given niches. Among dental NCPs, dentine sialophosphoprotein (DSPP) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family, whose members share common biochemical characteristics such as an Arg-Gly-Asp (RGD) motif. DSPP expression is cell- and tissue-specific and highly seen in odontoblasts and dentine. DSPP mutations cause hereditary dentine diseases. DSPP is catalysed into dentine glycoprotein (DGP)/sialoprotein (DSP) and phosphoprotein (DPP) by proteolysis. DSP is further processed towards active molecules. DPP contains an RGD motif and abundant Ser-Asp/Asp-Ser repeat regions. DPP-RGD motif binds to integrin αVß3 and activates intracellular signalling via mitogen-activated protein kinase (MAPK) and focal adhesion kinase (FAK)-ERK pathways. Unlike other SIBLING proteins, DPP lacks the RGD motif in some species. However, DPP Ser-Asp/Asp-Ser repeat regions bind to calcium-phosphate deposits and promote hydroxyapatite crystal growth and mineralisation via calmodulin-dependent protein kinase II (CaMKII) cascades. DSP lacks the RGD site but contains signal peptides. The tripeptides of the signal domains interact with cargo receptors within the endoplasmic reticulum that facilitate transport of DSPP from the endoplasmic reticulum to the extracellular matrix. Furthermore, the middle- and COOH-terminal regions of DSP bind to cellular membrane receptors, integrin ß6 and occludin, inducing cell differentiation. The present review may shed light on DSPP roles during odontogenesis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34073581

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, has been detected in breast milk in many countries; however, whether phthalate metabolite concentration and the detection rate in breast milk change postpartum is still unknown. We measured phthalate metabolite concentrations in breast milk in the first 6 months postpartum in women enrolled in the E-Da hospital from January to July 2017. A total of 56 breastfeeding mothers and 66 samples were included in this study. We analyzed the samples' concentration of eight phthalate metabolites using liquid chromatography mass spectrometry. The concentration of mono-2-ethylhexyl phthalate (MEHP) was significantly higher in the first month, and then decreased over time. The detection rate of ono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MBP) was low in the first month and then increased over time. Compared with a previous study published in 2011, the levels of MEHP and MiBP in breast milk were much lower in the present study, suggesting an increased awareness of the health risks of phthalate exposure after a food scandal occurred in Taiwan. This study provides information for evaluating newborns' exposure to different kinds of phthalate through human milk in the postpartum period.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Exposição Ambiental/análise , Poluentes Ambientais/análise , Feminino , Humanos , Recém-Nascido , Leite Humano/química , Ácidos Ftálicos/análise , Período Pós-Parto , Taiwan
11.
Nutrients ; 13(5)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063157

RESUMO

Maternal nutrition intake during pregnancy may affect the mother-to-child transmission of bacteria, resulting in gut microflora changes in the offspring, with long-term health consequences in later life. Longitudinal human studies are lacking, as only a small amount of studies showing the effect of nutrition intake during pregnancy on the gut microbiome of infants have been performed, and these studies have been mainly conducted on animals. This pilot study explores the effects of high or low fruit and vegetable gestational intake on the infant microbiome. We enrolled pregnant women with a complete 3-day dietary record and received postpartum follow-up. The 16S rRNA gene sequence was used to characterize the infant gut microbiome at 2 months (n = 39). Principal coordinate analysis ordination revealed that the infant gut microbiome clustered differently for high and low maternal fruit and vegetable consumption (p < 0.001). The linear discriminant analysis effect size and feature selection identified 6 and 17 taxa from both the high and low fruit and vegetable consumption groups. Among the 23 abundant taxa, we observed that six maternal intake nutrients were associated with nine taxa (e.g., Erysipelatoclostridium, Isobaculum, Lachnospiraceae, Betaproteobacteria, Burkholderiaceae, Sutterella, Clostridia, Clostridiales, and Lachnoclostridium). The amount of gestational fruit and vegetable consumption is associated with distinct changes in the infant gut microbiome at 2 months of age. Therefore, strategies involving increased fruit and vegetable consumption during pregnancy should be employed for modifying the gut microbiome early in life.


Assuntos
Dieta/estatística & dados numéricos , Frutas , Microbioma Gastrointestinal/genética , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Verduras , Adulto , Estudos de Coortes , Inquéritos sobre Dietas , Fezes/microbiologia , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Projetos Piloto , Gravidez , RNA Ribossômico 16S/análise
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(5): 633-639, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34134948

RESUMO

OBJECTIVE: To investigate the recurrence of ankylosing spondylitis (AS) that has been relieved by standard-dose adalimumab (ADA) after dose reduction or withdrawal of tumor necrosis factor-α inhibitor (TNFi) and explore the factors that predict AS occurrence. OBJECTIVE: This study was conducted among 63 patients with AS who reduced the dose of or discontinued TNFi after completing at least 12 treatment cycles with ADA (40 mg/2 weeks) to achieve ASAS20 improvement with a BATH disease activity index (BASDAI) < 4 for more than 8 weeks. The patients were followed up every 12 weeks for a total of 52 weeks, and the recurrence of AS, changes of BASDAI, C-reactive protein (CRP)-based disease activity score (ASDASCRP), low back pain (LBP) score, Bath Ankylosing Spondylitis Metrology Index (BASMI), CRP and ESR were recorded and analyzed. Cox regression model and ROC curve analyses were performed to analyze the risk factors of AS relapse after dose reduction or discontinuation of TNFi. OBJECTIVE: Of the 63 patients enrolled, 57 completed the follow-up study, among whom 22 (38.6%) patients experienced AS relapse within 52 weeks, with a median clinical recurrence time of 31 weeks. The recurrence rate of AS was significantly higher in patients with complete withdrawal of medications (89.0%) than in those with TNFi dose reduction and TNFi discontinuation (P < 0.001), and did not differ significantly between the latter two groups of patients (χ2= 0.071, P=0.791). The Cox regression model showed that a high baseline LBP score (HR=1.438, P=0.027) and a high BASMI score (HR=1.29, P=0.049) were the risk factors for AS recurrence after TNFi dose reduction or discontinuation, while maintenance of medication during follow-up was a protective factor (HR=0.209, P=0.001). ROC curve analysis showed that the combination of baseline LBP score, BASMI and medication during follow-up had a good predictive value for AS relapse (AUC=0.819) with a sensitivity of 0.772 and a specificity of 0.718. OBJECTIVE: Dose reduction or discontinuation of TNFi is associated with a high recurrence rate of AS that has been relieved by TNFi treatment. A high LBP score, a high BASMI score and discontinuation of maintenance medication are the risk factors for AS recurrence in patients after dose reduction or withdrawal of TNFi.


Assuntos
Antirreumáticos , Espondilite Anquilosante , Antirreumáticos/uso terapêutico , Seguimentos , Humanos , Recidiva , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento , Fator de Necrose Tumoral alfa
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(5): 729-735, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34134961

RESUMO

OBJECTIVE: To investigate the protective effect of luteolin against cadmium (Cd)-induced injury in human lung epithelial Beas-2B cells. OBJECTIVE: Beas-2B cells were treated with different concentrations of luteolin (0-160 µmol/L) or Cd (0-40 µmol/L) for 24 h, and the cell viability was examined using MTT assay. After treatment with luteolin (0.25, 0.5 and 0.75 µmol/L) with or without Cd (5 µmol/L) for 24 h, the cells were examined for viability, lactate dehydrogenase (LDH) activity and morphological changes of the cell nuclei using Hoechst fluorescent staining. The levels of ROS, SOD, GSH and MDA in the treated cells were detected, and the expression levels of Akt, p-Akt and nuclear factor E2-related factor 2 (Nrf2) proteins were determined using Western blotting. OBJECTIVE: Luteolin within the concentration range of 0-80 µmol/L did not significantly affect the survival rate of Beas-2B cells (P>0.05), but Cd at 5 µmol/L significantly decreased the cell viability (P < 0.05) with an IC50 of 24.6 µmol/L. In Cd-treated cells, treatment with luteolin significantly mitigated the decrease of cell viability, reduced LDH release and cell apoptosis, enhanced SOD activity and GSH content, and inhibited the production of MDA and ROS (all P < 0.05). Luteolin also significantly up-regulated the expression levels of p-Akt and Nrf2 protein in Cd-treated Beas-2B cells (P < 0.05). OBJECTIVE: Luteolin has a significant protective effect against Cd-induced injury in Beas-2B cells, and the effects are probably mediated, at least in part, by promoting the activation of Akt and Nrf2.


Assuntos
Cádmio , Luteolina , Apoptose , Cádmio/toxicidade , Células Epiteliais/metabolismo , Humanos , Pulmão/metabolismo , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(5): 754-759, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34134964

RESUMO

OBJECTIVE: To investigate the anatomy of the perforator vessels of the deep circumflex iliac artery (DCIA) and the techniques for repairing mandibular complex defect using chimeric deep circumflex iliac artery perforator flap (DCIAPF). OBJECTIVE: We analyzed the origin, distribution, number and courses of the perforator vessels of the DCIA, and measured the outside diameters of the vessels at the origin in 6 adult cadaveric specimens (12 sides) with latex perfusion. From July, 2018 to September, 2019, based on the results of anatomical study and imaging findings and using the digital surgical guide plate, we harvested DCIAPF from 4 patients for repairing mandibular body or angle defects and oral soft tissue defects. OBJECTIVE: The perforating vessels of the DCIA included abdominal muscular branches, osteomusculocutaneous branches and terminal musculocutaneous branches. The abdominal muscle branches originated from the DCIA inguinal segment in 4 and from both the inguinal and iliac segments in 2 of the specimens. The osteomusculocutaneous branches all originated from the internal iliac crest in 75% and from both the inguinal and internal iliac crest segments in 25% of cases; the inguinal segment gave rise to only one perforating branch. The number of the musculocutaneous perforating branches was 1 (58.3%) or 2 (41.7%). In the 4 patients undergoing mandibular reconstruction, the DCIAPF survived in all cases with good recovery of the donor site wound. Satisfactory facial appearance with good oral morphology and occlusal relationship was achieved at 1 month postoperatively in all the patients. None of the patients experienced obvious functional abnormalities at the donor site, and imaging examination confirmed successful reconstruction of the oromandibular defects in all the cases. OBJECTIVE: A good understanding of the anatomic characteristics of the perforator vessels of the DCIA combined with imaging examinations and digital surgery technology facilitates the harvest of DCIAPF for repairing mandibular body or angle defects complicated by oral soft tissue defects.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Adulto , Humanos , Artéria Ilíaca/cirurgia , Ílio , Mandíbula/cirurgia , Retalho Perfurante/cirurgia
15.
Neurosci Lett ; 758: 136011, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34090936

RESUMO

Neuronal hyperactivity is an early, common manifestation of Alzheimer's disease (AD), and is believed to drive AD progression. Neuronal hyperactivity in the form of baseline activity (or spontaneous Ca2+ transients) has consistently been demonstrated in mouse models of AD using two-photon in vivo Ca2+ imaging of cortical or hippocampal neurons in anesthetized animals. Notably, these AD-related spontaneous Ca2+ transients were hardly detected in acute hippocampal slices, probably due to neuronal damage during brain slicing. To better preserve neuronal activity, we employed the N-methyl-D-glucamine (NMDG) protective brain slicing protocol. We performed confocal in vitro Ca2+ imaging of hippocampal CA1 neurons in optimized hippocampal slices. Consistent with previous in vivo studies, our in vitro studies using optimized brain slices also showed that limiting the open duration of the ryanodine receptor 2 (RyR2) by the RyR2 mutation E4872Q or by the R-carvedilol enantiomer prevented and rescued neuronal hyperactivity of hippocampal CA1 neurons from 5xFAD mice. Thus, genetically and pharmacologically limiting RyR2 open time prevented and rescued AD-related neuronal hyperactivity in vitro in optimized brain slices in the absence of anesthetics' influence. Our data also suggest that the NMDG protective brain slicing preparation offers an alternative means to study neuronal hyperactivity of various cell types in different brain regions, especially in regions that are not readily accessible to two-photon in vivo Ca2+ imaging.

16.
Curr Fungal Infect Rep ; : 1-11, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34178208

RESUMO

Purpose of Review: This review summarises the epidemiology of Candida auris infection and describes contemporary and emerging diagnostic methods for detection and identification of C. auris. Recent Findings: A fifth C. auris clade has been described. Diagnostic accuracy has improved with development of selective/differential media for C. auris. Advances in spectral databases of matrix-associated laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) systems have reduced misidentification. Direct detection of C. auris in clinical specimens using real time PCR is increasingly used, as is whole genome sequencing (WGS) to track nosocomial spread and to study phylogenetic relationships and drug resistance. Summary: C. auris is an important transmissible, nosocomial pathogen. The microbiological laboratory diagnostic capacity has extended beyond culture-based methods to include PCR and WGS. Microbiological techniques on the horizon include the use of MALDI-TOF MS for early echinocandin antifungal susceptibility testing (AST) and expansion of the versatile and information-rich WGS methods for outbreak investigation.

17.
Br J Dermatol ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34184254

RESUMO

Advance care planning (ACP) and code status (CS) discussions may enhance outcomes among patients with serious illness.1 Despite growing evidence for the benefits of ACP and CS, utilization patterns remain under-evaluated for dermatoses associated with increased mortality, such as bullous pemphigoid (BP).2 To address this gap, we assessed change over time in ACP and CS among a cohort of newly-diagnosed BP patients, additionally characterizing survival outcomes and intensity of end-of-life care.

18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(3): 590-593, 2021 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-34145866

RESUMO

OBJECTIVE: To analyze the clinical characteristics of 170 cases of macrodactyly. METHODS: Medical records of 170 macrodactyly patients at Beijing Jishuitan Hospital between March 2006 and October 2019, including demographic characteristics, clinical presentations, anatomical distributions, X-rays, pathological findings, and treatments, were reviewed. PIK3CA mutation analyses of 12 patients were also reviewed. RESULTS: Disease incidence was similar across sex and geographical regions. Multiple-digit involvement was 3.9 times more frequent than single-digit involvement. In upper deformit: ies, the index finger, middle finger and thumb were mostly involved, and the second and third toes were the most affected on the foot. Two digits were affected more often than three digits, with the affected multiple digits were adjacent most time. The cases of progressive macrodactyly, in which the affected digits grew at a faster rate than the unaffected digits, were found more than static type. Most of progressive macrodactyly were noticed at birth. In terms of nerve involvement, affected fingers mostly occurred in the median nerve innervation area (79.4%) accompanied by median nerve and brunches enlargement and fat infiltration, i.e., nerve territory oriented; affected toes mostly occurred in the medial plantar nerve innervation area (89.1%), marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth, i.e., lipomatous. Only 17 cases had comorbid of syndactyly. The metacarpal bones were involved only in progressive type of macrodactyly. Ten of the 12 cases subjected to PIK3CA mutation analysis were positive. Among all tested specimens, PIK3CA mutation levels ranged from 7% to 27%. In terms of tissue sources in which a mutation was found, adipose tissue had the highest mutation detection rate, followed by nerve and skin. All the DNA samples of blood from the 12 PIK3CA mutation-positive patients were negative. CONCLUSION: Macrodactyly fingers mostly occurred in the median nerve innervation area accompanied by median nerve and brunches enlargement and fat infiltration. The index and middle fingers were mostly involved. Macrodactyly toes mostly occurred in the medial plantar nerve innervation area, marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth. The second and third toes were the most affected on the foot. A high proportion (83%) of isolated macrodactyly patients carry activating PIK3CA mutations. Adipose, nerve, and skin tissues provide the highest PIK3CA mutation detection yield among all types of tissue studied.


Assuntos
Deformidades Congênitas dos Membros , Análise Mutacional de DNA , Dedos/anormalidades , Humanos , Recém-Nascido , Mutação , Dedos do Pé
19.
Zhonghua Gan Zang Bing Za Zhi ; 29(5): 484-487, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34107591

RESUMO

Chronic liver diseases caused by a variety of causes can lead to the formation of liver fibrosis, and further develop into liver cirrhosis, which is a serious threat to human life and health. As a new research field, lipidomics has been developing vigorously in recent years and has shown great potential in the field of liver fibrosis research. This article introduces lipidomics technology, and discusses its pathogenesis, lipotoxicity biomarkers and emerging therapeutic targets, so as to provide a prospects for the future development of lipidomics in the field of liver fibrosis.


Assuntos
Lipidômica , Hepatopatias , Biomarcadores , Humanos , Metabolismo dos Lipídeos , Cirrose Hepática
20.
Integr Comp Biol ; 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34117763

RESUMO

Males in many species engage in physical combat over access to mates, and sexual selection has led to the evolution of weapons to enhance contest performance. The size of these often-elaborate structures is known to be exquisitely sensitive to nutrition. However, we know very little about the degree to which nutrition affects other attributes of animal weapons that can be crucial to fighting. In this study, we investigated the impact of natural dietary variation on weapon structural integrity in a fighting insect, Narnia femorata (Hemiptera: Coreidae). Males in this species display their enlarged, spiny hind legs to other males, and these legs serve as weapons in aggressive physical contests where they are used to strike and squeeze opponents. N. femorata feeds on the fruit of prickly pear cactus and sets up territories on this plant. In North Central Florida the prickly pear Opuntia mesacantha spp. lata blooms and begins to produce fruits in April and May. N. femorata has multiple, overlapping generations while the green fruits slowly ripen over the next several months. We examined insects reaching adulthood at two nearby time points in this range, June and July, to test the influence of the nutrition provided by ripening green cactus fruit on weapon size and its ability to resist puncture. We also raised insects on cactus with red, ripe fruit for comparison. We found a striking effect of cactus fruit phenology on weapons. Insects raised with the more mature green fruit (those in the second cohort) had 71% larger weapon area and 4.4 times greater puncture resistance than those raised on the early green fruit (those in the first cohort). In contrast, insects raised on red, ripe fruit were moderate in size, had high puncture resistance, and they changed little phenotypically from the first to second cohort. Increased structural integrity of the hind femur weapon was associated with the increased body size that came with better nutrition. This pattern highlights that cuticle thickness increased or its material properties changed when weapons were larger. Importantly, effects of nutrition on puncture resistance also transcended size. Insects of the same size had greater structural integrity if they received superior nutrition. Sexually selected weapons are often used as visual signals to conspecifics before fights, and this work hints that the size of the weapons may be a poor signal of weapon performance when nutrition is variable.

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