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1.
J Immunol ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507947

RESUMO

Sepsis is a life-threatening organ dysfunction caused by a dysfunctional host response to infection. Neutrophils play a protective role by releasing antibacterial proteins or by phagocytizing bacteria. However, excess neutrophils can induce tissue damage. Recently, a novel intercellular communication pathway involving extracellular vesicles (EVs) has garnered considerable attention. However, whether EVs secreted by macrophages mediate neutrophil recruitment to infected sites has yet to be studied. In this study, we assessed the chemotactic effect of EVs isolated from mouse Raw264.7 macrophages on mouse neutrophils and found that CXCL2 was highly expressed in these EVs. By regulating CXCL2 in Raw264.7 macrophages, we found that CXCL2 on macrophage EVs recruited neutrophils in vitro and in vivo. The CXCL2 EVs activated the CXCR2/PKC/NOX4 pathway and induced tissue damage. This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.

2.
Environ Pollut ; 291: 118094, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517175

RESUMO

Indoor air quality ((IAQ) in classrooms was associated with the daily exposure of school-age children who are particularly vulnerable to air pollutants exposure, while few data exist to evaluate classroom indoor air quality nationwide in China. The subsample of the CIEHS 2018 study was performed in 66 classrooms of 22 primary schools nationwide in China. Temperature, relative humidity, PM2.5, PM10, CO2, CO, formaldehyde concentrations, bacteria and fungi were detected in all classrooms by using the instruments that meet the specified accuracy. The ratios of indoor to outdoor (I/O) of PM2.5 were calculated in each classroom to identify whether the indoor environment the pollutants comes from outdoors. The indoor PM2.5, PM10, CO, HCHO, bacteria and fungi GM concentration are 47.40 µg/m3, 72.91 µg/m3, 0.37 mg/m3, 0.02 mg/m3, 347.51 CFU/m3 and 362.76 CFU/m3, respectively. We observed that there were 66.5%, 52.6%, 22.4%, 1.8%, and 9.6% of the classrooms that exceeded the guideline values of PM2.5, PM10, CO2, HCHO, and bacteria, respectively. It should be attention that all of the classroom's PM2.5 concentrations in Shijiazhuang and Nanning, PM10 concentrations in Nanning, CO2 concentration in Lanzhou were exceeded the suggested values. Bacteria contamination in Shijiazhuang's classrooms is also serious. All classroom CO concentrations meet the requirement. The results indicated that classroom indoor PM2.5 was significantly positively correlated with indoor PM10 and CO2, while was negative correlated with temperature, CO, and fungi. Our results suggest that indoor air pollution in classrooms was a severe problem in Chinese primary schools. It is necessary to strengthen ventilation in the classroom to improve indoor air quality. What's more, a healthy learning environment should be created for primary school students.

3.
Nat Nanotechnol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531557

RESUMO

Converting CO2 emissions, powered by renewable electricity, to produce fuels and chemicals provides an elegant route towards a carbon-neutral energy cycle. Progress in the understanding and synthesis of Cu catalysts has spurred the explosive development of electrochemical CO2 reduction (CO2RR) technology to produce hydrocarbons and oxygenates; however, Cu, as the predominant catalyst, often exhibits limited selectivity and activity towards a specific product, leading to low productivity and substantial post-reaction purification. Here, we present a single-atom Pb-alloyed Cu catalyst (Pb1Cu) that can exclusively (~96% Faradaic efficiency) convert CO2 into formate with high activity in excess of 1 A cm-2. The Pb1Cu electrocatalyst converts CO2 into formate on the modulated Cu sites rather than on the isolated Pb. In situ spectroscopic evidence and theoretical calculations revealed that the activated Cu sites of the Pb1Cu catalyst regulate the first protonation step of the CO2RR and divert the CO2RR towards a HCOO* path rather than a COOH* path, thus thwarting the possibility of other products. We further showcase the continuous production of a pure formic acid solution at 100 mA cm-2 over 180 h using a solid electrolyte reactor and Pb1Cu.

4.
Radiat Oncol ; 16(1): 179, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535161

RESUMO

PURPOSE/OBJECTIVE(S): The purpose of the study was to assess the uterus motions and bladder volume changes of fractional movements in cervical sites throughout the external beam radiotherapy (EBRT) treatment. MATERIALS/METHODS: A prospective online MR imaging tracking study was conducted in EBRT 43 patients with at least 4 scans during each treatment (before: ultrasound scan, MRI scan, CBCT scan, after: MRI scan) were included. In order to improve the treatment repeatability, each patient was instructed to empty the bladder and drink 500 ml water 1 h before CT simulation and each treatment. If the ultrasound scan result reached the CT simulation volume of bladder, the treatment began. Bladder was outlined on the T2 weighted axial sequence and CBCT image by the two observers to avoid the influence of contouring. The data of bladder volume and scanning time were accurately recorded. The bladder volumes, filling rates and uterus motion were retrospectively analyzed by MIM software. RESULTS: Inter-fraction variation of the bladder volume was significant (p < 0.0001). Intra-fraction mean increase of the bladder volume was modest (30 cc) but significant (p < 0.001). Both inter- and intra-fraction of the uterus motion were significant. The average time between the pre-and post-fraction MRI scans was 27.82 ± 7.12 min (range 10-55 min) for IMRT plans and 24.14 ± 5.86 min (range7-38 min) for VMAT plan. Average bladder filling rate was 3.43 ml/min. The bladder filling rate did not change significantly with the course of treatment, but the bladder was more intolerant. CONCLUSION: This is the most detailed assessment of intra-fraction and inter-fraction motion during EBRT for cervical cancer. Finally, this study will inform appropriate treatment margins for online adaptive radiotherapy. We suggest that at least one image scan is needed before the EBRT. The portable US scanner provides a quick but unreliable measurement of the bladder volume. There is a significant statistical difference between the results of ultrasonic scanning and that of image scanning.

5.
BMC Med Genomics ; 14(1): 222, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511133

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with neuronal cell inclusions composed of neurofilaments and other abnormal aggregative proteins as pathological hallmarks. Approximately 90% of patients have sporadic cases (sALS), and at least 4 genes, i.e. C9orf72, SOD1, FUS and TARDBP, have been identified as the main causative genes, while many others have been proposed as potential risk genes. However, these mutations could explain only ~ 10% of sALS cases. The neurofilament polypeptides encoded by NEFH, NEFM, and NEFL are promising protein biomarkers for ALS and other degenerative diseases. However, whether the genetic variants of these genes were associated with ALS remain ambiguous. METHODS: Here, we used PCR-Sanger to sequence the exons of these three genes in a cohort of 371 sALS patients and 711 healthy controls (Phase I) and validated the risk variant in another 300 sALS patients and 1076 controls (Phase II). RESULTS: A total of 92 variants were identified, including 36 rare heterozygous variants in NEFH, 27 in NEFM, and 16 in NEFL, and only rs568759161 (p.Ser787Arg) in NEFH reached nominal statistical power (P = 0.02 at Phase I, P = 0.009 at Phase II) in the case-control comparison. Together, the Phase I and II studies showed the significantly higher frequency of the variant in cases (9/1342, 0.67%) than in controls (2/3574, 0.07%) (OR 12.06; 95% CI 2.60-55.88; P = 0.0003). No variants passed multiple testing in the discovery cohort, but rs568759161 was associated with ALS in a replication cohort. CONCLUSIONS: Our results confirmed that NEFH Ser787Arg is a novel sALS risk variant in Chinese subjects, but NEFM and NEFL were not associated with sALS. These data may have implications for genetic counselling and for understanding the pathogenesis of sALS.

6.
Microbiol Spectr ; : e0050921, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523996

RESUMO

Liberibacter pathogens are the causative agents of several severe crop diseases worldwide, including citrus Huanglongbing and potato zebra chip. These bacteria are endophytic and nonculturable, which makes experimental approaches challenging and highlights the need for bioinformatic analysis in advancing our understanding about Liberibacter pathogenesis. Here, we performed an in-depth comparative phylogenomic analysis of the Liberibacter pathogens and their free-living, nonpathogenic, ancestral species, aiming to identify major genomic changes and determinants associated with their evolutionary transitions in living habitats and pathogenicity. Using gene neighborhood analysis and phylogenetic classification, we systematically uncovered, annotated, and classified all prophage loci into four types, including one previously unrecognized group. We showed that these prophages originated through independent gene transfers at different evolutionary stages of Liberibacter and only the SC-type prophage was associated with the emergence of the pathogens. Using ortholog clustering, we vigorously identified two additional sets of genomic genes, which were either lost or gained in the ancestor of the pathogens. Consistent with the habitat change, the lost genes were enriched for biosynthesis of cellular building blocks. Importantly, among the gained genes, we uncovered several previously unrecognized toxins, including new toxins homologous to the EspG/VirA effectors, a YdjM phospholipase toxin, and a secreted endonuclease/exonuclease/phosphatase (EEP) protein. Our results substantially extend the knowledge of the evolutionary events and potential determinants leading to the emergence of endophytic, pathogenic Liberibacter species, which will facilitate the design of functional experiments and the development of new methods for detection and blockage of these pathogens. IMPORTANCE Liberibacter pathogens are associated with several severe crop diseases, including citrus Huanglongbing, the most destructive disease to the citrus industry. Currently, no effective cure or treatments are available, and no resistant citrus variety has been found. The fact that these obligate endophytic pathogens are not culturable has made it extremely challenging to experimentally uncover the genes/proteins important to Liberibacter pathogenesis. Further, earlier bioinformatics studies failed to identify key genomic determinants, such as toxins and effector proteins, that underlie the pathogenicity of the bacteria. In this study, an in-depth comparative genomic analysis of Liberibacter pathogens along with their ancestral nonpathogenic species identified the prophage loci and several novel toxins that are evolutionarily associated with the emergence of the pathogens. These results shed new light on the disease mechanism of Liberibacter pathogens and will facilitate the development of new detection and blockage methods targeting the toxins.

7.
Inflammation ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480249

RESUMO

Supervillin (SVIL) is an actin-binding and membrane-associated protein, which belongs to villin/gelsolin family. It has been reported that SVIL was involved in the regulation of macrophages' movement and lipopolysaccharide (LPS) increased the SVIL mRNA expression in neutrophils, but the underlying mechanisms remain unknown. This work investigated the underlying molecular mechanisms of LPS regulating SVIL expression in macrophages and hence the possible role of SVIL in LPS-induced inflammation. We found that in THP-1-derived macrophages, LPS obviously increased SVIL mRNA and protein expression. Inhibition of TLR4 by Resatorvid (Res) remarkably reversed the LPS-induced SVIL expression. Additionally, inhibition of ERK1/2 signaling pathway (by U0126 or GDC-0994) and NF-κB (by BAY) significantly reduced the LPS-induced SVIL expression. Interestingly, down-regulation of SVIL by SVIL-specific shRNAs significantly attenuated the expression of IL-6, IL-1ß & TNF-α induced by LPS at both mRNA and protein levels. Furthermore, we also observed that SVIL knockdown decreased the proportion of cells in G2/M phase and increased the proportion of cells in S & G0-1 phase of THP-1 derived macrophages, but did not influence the cell viability. Taken together, we demonstrated that LPS induced the expression of SVIL via activating TLR4/NF-κB and ERK1/2 MAPK pathways, and SVIL participated in the inflammatory response of LPS-induced IL-6, IL-1ß and TNF-α upregulation in macrophages.

8.
J Med Chem ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491761

RESUMO

The epidermal growth factor receptor (EGFR) harboring activating mutations is a clinically validated target in non-small-cell lung cancer, and a number of inhibitors of the EGFR tyrosine kinase domain, including osimertinib, have been approved for clinical use. Resistance to these therapies has emerged due to a variety of molecular events including the C797S mutation which renders third-generation C797-targeting covalent EGFR inhibitors considerably less potent against the target due to the loss of the key covalent-bond-forming residue. We describe the medicinal chemistry optimization of a biochemically potent but modestly cell-active, reversible EGFR inhibitor starting point with sub-optimal physicochemical properties. These studies culminated in the identification of compound 12 that showed improved cell potency, oral exposure, and in vivo activity in clinically relevant EGFR-mutant-driven disease models, including an Exon19 deletion/T790M/C797S triple-mutant mouse xenograft model.

9.
Parasit Vectors ; 14(1): 452, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488869

RESUMO

BACKGROUND: Despite the medical importance of mosquitoes of the genus Anopheles in the transmission of malaria and other human diseases, its phylogenetic relationships are not settled, and the characteristics of mitochondrial genome (mitogenome) are not thoroughly understood. METHODS: The present study sequenced and analyzed the complete mitogenomes of An. peditaeniatus and An. nitidus, investigated genome characteristics, and inferred the phylogenetic relationships of 76 Anopheles spp. RESULTS: The complete mitogenomes of An. peditaeniatus and An. nitidus are 15,416 and 15,418 bp long, respectively, and both include 13 PCGs, 22 tRNAs, two tRNAs and one control region (CR). Mitogenomes of Anopheles spp. are similar to those of other insects in general characteristics; however, the trnR and trnA have been reversed to "trnR-trnA," as has been reported in other mosquito genera. Genome variations mainly occur in CR length (493-886 bp) with six repeat unit types identified for the first time that demonstrate an evolutionary signal. The subgenera Lophopodomyia, Stethomyia, Kerteszia, Nyssorhynchus, Anopheles and Cellia are inferred to be monophyletic, and the phylogenetic analyses support a new phylogenetic relationship among the six subgenera investigated, in that subgenus Lophopodomyia is the sister to all other five subgenera, and the remaining five subgenera are divided into two clades, one of which is a sister-taxon subgenera Stethomyia + Kerteszia, and the other consists of subgenus Nyssorhynchus as the sister to a sister-group subgenera Anopheles + Cellia. Four series (Neomyzomyia, Pyretophorus, Neocellia and Myzomyia) of the subgenus Cellia, and two series (Arribalzagia and Myzorhynchus) of the subgenus Anopheles were found to be monophyletic, whereas three sections (Myzorhynchella, Argyritarsis and Albimanus) and their subdivisions of the subgenus Nyssorhynchus were polyphyletic or paraphyletic. CONCLUSIONS: The study comprehensively uncovered the characteristics of mitogenome and the phylogenetics based on mitogenomes in the genus Anopheles, and provided information for further study on the mitogenomes, phylogenetics and taxonomic revision of the genus.

10.
Chin Med J (Engl) ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34483252

RESUMO

BACKGROUND: Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis. METHODS: In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-ß (TGF-ß), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student's t test or analysis of variance were used for statistical analysis. RESULTS: In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ±â€Š0.02 vs. 0.07 ±â€Š0.02, t = 8.66, P = 0.001), TGF-ß (0.54 ±â€Š0.05 vs. 0.09 ±â€Š0.06, t = 10.00, P < 0.001), p-Smad2/3 (0.58 ±â€Š0.06 vs. 0.07 ±â€Š0.03, t = 12.86, P < 0.001) and α-collagen I (0.27 ±â€Š0.02 vs. 0.16 ±â€Š0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ±â€Š7.32 vs. 9.56 ±â€Š1.68, t = 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ±â€Š0.15 vs. 1.00 ±â€Š0.10, t = 4.32, P = 0.012), AT1R (4.05 ±â€Š0.64 vs. 1.00 ±â€Š0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ±â€Š0.36 vs. 1.00 ±â€Š0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production. CONCLUSIONS: Exosomes mediated intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.

11.
Mol Brain ; 14(1): 140, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526080

RESUMO

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice. The enhancement was long-lasting, and persisted for at least 3 h. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase Mζ (PKMζ). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.

12.
Pediatr Infect Dis J ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34508026

RESUMO

BACKGROUND: China has a high burden of tuberculosis and latent tuberculosis infection (LTBI). The aim of this study was to estimate the prevalence of LTBI among healthy young children and adolescents and test a 2-step approach to explore the threshold for the diagnosis of tuberculosis infection in Chengdu, China. METHODS: Healthy preschool children and school-going children in Chengdu, Sichuan Province, were screened for LTBI using the tuberculin skin test (TST). Preschool children with TST ≥ 5 mm also underwent interferon-γ release assay (IGRA) to explore the threshold of this 2-step approach. RESULTS: In total, 5667 healthy young children and adolescents completed TST test between July 2020 and January 2021 and were included in the present analysis. The age of the participants ranged from 2.4 to 18 years (median 7.25 ± 4.514 years), of which 2093 (36.9%) were younger than 5 years. The overall prevalence of LTBI was 6.37% and 6.64% in children younger than 5 years old. Fourteen of the 341 preschool children with TST ≥5 mm were interferon-γ release assay positive, of which 4 showed a TST result of 5-10 mm, and 6 preschool children received preventive treatment for LTBI. CONCLUSIONS: Healthy young children and adolescents should also be considered as important target populations for LTBI screening. TST can be recommended for first-line screening as part of a 2-step approach for LTBI screening using a positive threshold of 5 mm.

13.
Pharmacol Res ; 172: 105857, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34461223

RESUMO

Opioid relapse is generally caused by the recurrence of context-induced memory reinstatement of reward. However, the internal mechanisms that facilitate and modify these processes remain unknown. One of the key regions of the reward is the nucleus accumbens (NAc) which receives glutamatergic projections from the dorsal hippocampus CA1 (dCA1). It is not yet known whether the dCA1 projection to the NAc shell regulates the context-induced memory recall of morphine. Here, we used a common model of addiction-related behavior conditioned place preference paradigm, combined with immunofluorescence, chemogenetics, optogenetics, and electrophysiology techniques to characterize the projection of the dCA1 to the NAc shell, in context-induced relapse memory to morphine. We found that glutamatergic neurons of the dCA1 and gamma aminobutyric acidergic (GABA) neurons of the NAc shell are the key brain areas and neurons involved in the context-induced reinstatement of morphine memory. The dCA1-NAc shell glutamatergic input pathway and the excitatory synaptic transmission of the dCA1-NAc shell were enhanced via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) when mice were re-exposed to environmental cues previously associated with drug intake. Furthermore, chemogenetic and optogenetic inactivation of the dCA1-NAc shell pathway decreased the recurrence of long- and short-term morphine-paired context memory in mice. These results provided evidence that the dCA1-NAc shell glutamatergic projections mediated the context-induced memory recall of morphine.

14.
Comput Biol Med ; 136: 104769, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34426169

RESUMO

Previous studies have shown that Sophorae Tonkinensis radix et rhizome (ST) can be used to treat some lung diseases. However, the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST treatment of lung diseases remain unclear. Thus, the aim of this study was to carry out an integrated analysis based on the biolabel-led research pattern. Proteomics and metabonomics were applied to explore the biolabels responsible for the effect of ST on lung tissue. Based on the biolabels, a bioinformatics database was used to topologically analyze the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST in treating lung diseases. Four human lung-cancer cell models were used to validate the results of the biolabel analysis. In total, 45 proteins and 3 metabolites were significantly enriched in 13 pathways and were considered as biolabels. Bioinformatics revealed that the therapeutic potentials of ST involved a variety of lung diseases, especially lung neoplasms. Under the mediation of 40 biolabels, 29 compounds may be the material basis of ST in treating lung diseases. In a verification experiment, ST had a significant inhibitory effect on the H226 cell line (lung squamous cell carcinoma), which ranks first in morbidity and mortality among lung cancers in China. Additionally, five biolabels (CPS1, CKM, CPT1B, COX5B, and COX4I1) were involved in the anti-lung cancer mechanism of ST and 3 compounds (gallic acid, betulinic acid, and caffeic acid). These findings indicate that the biolabel-led research pattern was helpful in achieving the objectives of this study.

15.
Sci Total Environ ; 800: 149480, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34392211

RESUMO

Wastewater based epidemiology (WBE) has been successfully applied for SARS-CoV-2 surveillance at the city and building levels. However, sampling at the city level does not provide sufficient spatial granularity to identify COVID-19 hotspots, while data from building-level sampling are too narrow in scope for broader public health application. The objective of this study was to examine the feasibility of using wastewater from wastewater collection systems (WCSs) to monitor COVID-19 hotspots at the zip code level. In this study, 24-h composite wastewater samples were collected from five manholes and two wastewater treatment plants (WWTPs) in the City of Lincoln, Nebraska. By comparing to the reported weekly COVID-19 case numbers, we identified different hotspots responsible for two COVID-19 surges during the study period. One zip code was the only sampling locations that was consistently tested positive during the first COVID-19 surge. In comparison, nearly all the zip codes tested exhibited virus concentration increases that overlapped with the second COVID-19 surge, suggesting broader spread of the virus at that time. These findings demonstrate the feasibility of using WBE to monitor COVID-19 at the zip code level. Highly localized disease surveillance methods can improve public health prevention and mitigation measures at the community level.

16.
Obes Facts ; : 1-6, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34428761

RESUMO

INTRODUCTION: This study aimed to investigate whether neck circumference (NC) was associated with the incidence of type 2 diabetes in Chinese elderly individuals. METHODS: A community-based cohort study was conducted on elderly inhabitants in Shanghai with a mean age of 71.0 ± 5.8 years (n = 2,646). Binary logistic regression analysis was performed to evaluate the association between NC and the prevalence of type 2 diabetes, while a Cox regression model was used to determine the association between NC and the incidence of type 2 diabetes after a follow-up of 2 years. RESULTS: Logistic regression analysis showed that a larger NC was significantly associated with an increased risk for type 2 diabetes in men (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.07-1.31; p = 0.001) and women (OR 1.25, 95% CI 1.13-1.38; p < 0.001). Cox regression analysis revealed that NC was independently associated with the incidence of type 2 diabetes in both men (hazard ratio [HR] 1.14, 95% CI 1.05-1.23; p = 0.002) and women (HR 1.18, 95% CI 1.10-1.27; p < 0.001). CONCLUSIONS: A larger NC was associated with a higher risk of developing type 2 diabetes in Chinese elderly individuals. However, studies with larger sample sizes and longer follow-up durations are needed to definitively determine the relationship between NC and the risk of developing type 2 diabetes.

17.
Support Care Cancer ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432170

RESUMO

PURPOSE: Limited risk assessment tool to stratify the risk of PICC-related thrombosis (PICC-RVT) in breast cancer patients. This study developed a model to assess the risk of PICC-RVT in breast cancer patients. METHODS: We conducted a retrospective cohort study of 1284 breast cancer patients receiving PICC insertion from January 1, 2015, to August 31, 2019, at a cancer specialized hospital in Hunan province, China. The entire population was divided into two groups at a ratio of 3:1 which included a derivation sample (n = 978), and a validation sample (n = 284). PICC-RVT was confirmed by ultrasonography in the presence of clinical symptoms and signs. RESULTS: PICC-RVT occurred in 40 (4.09%) of the derivation sample patients. Multivariable analysis identified 9 variables: chronic obstructive pulmonary disease, prior central venous catheter placement, higher level of platelets, higher level of D-dimer, lower level of activated partial thromboplastin time, menopause, no prior breast surgery, upper extremity lymphedema, and endocrine therapy. Points were assigned to each variable according to regression coefficient. The model had an area under the receiver operating characteristics curve (AUC) of 0.850 (95% CI 0.776 to 0.924), The Hosmer-Lemeshow goodness-of-fit was 5.780 (p = 0.328). At a cutoff value of 3.5, the sensitivity and specificity were 75% and 83%, respectively. CONCLUSION: Several disease-specific factors of breast cancer (e.g., menopause, endocrine therapy, and upper extremity lymphedema) play important roles in the development of PICC-RVT. Patients at higher PICC-RVT risk could be candidates for close post-insertion monitoring and interventions to prevent PICC-RVT.

18.
AIDS Care ; : 1-6, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34402350

RESUMO

Adherence to antiretroviral therapy (ART) is a prerequisite to improve immunity and reduce the morbidity and mortality of people living with HIV (PLWH). To describe ART adherence and associated factors among PLWH, patients who initiated ART in Liuzhou between 1998 and 2013 were recruited. Socio-demographic characteristics, HIV infection-related characteristics and clinical tests were analyzed. Both descriptive and multi-level analyses were used to explore factors related to ART adherence of PLWH who initiated ART in Liuzhou. A total of 8433 patients were recruited in this study. The rate of adherence to ART was 84.9% in PLWH who initiated ART in Liuzhou between 1998 and 2013. The female sex, WHO clinical stage III or IV before ART initiation, longer treatment duration and higher triglyceride were positively associated with ART adherence. Meanwhile, HIV acquired by intravenous drug use, co-infection with tuberculosis and other opportunistic infections were negatively associated with ART adherence. Measures should be adopted to improve the ART adherence of PLWH who are male, acquired HIV by intravenous drug use, and are co-infected with tuberculosis and other opportunistic infections.

19.
Curr Med Sci ; 41(4): 815-820, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403107

RESUMO

OBJECTIVE: Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases. METHODS: A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children's Medical Center. RESULTS: All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge. CONCLUSION: This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.

20.
Neuropharmacology ; 197: 108749, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34364898

RESUMO

The anterior cingulate cortex (ACC) plays an important role in pain modulation, and pain-related emotional disorders. In the ACC, two major forms of long-term potentiation (LTP) coexist in excitatory synapses and lay the basis of chronic pain and pain-related emotional disorders. The induction of postsynaptic LTP is dependent on the activation of postsynaptic NMDA receptors (NMDARs), while the presynaptic LTP is NMDAR-independent. Long-term depression (LTD) can also be divided into two types according to the degree of sensitivity to the inhibition of NMDARs. NMDAR heteromers containing GluN2A and GluN2B act as key molecules in both the NMDAR-dependent postsynaptic LTP and LTD. Additionally, NMDARs also exist in presynaptic terminals and modulate the evoked and spontaneous transmitter release. From a translational point of view, inhibiting subtypes of NMDARs and/or downstream signaling proteins may provide potential drug targets for chronic pain and its related emotional disorders.

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