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1.
Eur Radiol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263361

RESUMO

OBJECTIVES: To evaluate whether the signal intensity ratio (rSI) of the draining vein on silent MR angiography is correlated with arteriovenous (A-V) transit time on digital subtraction angiography (DSA), thereby identifying high-flow A-V shunt in brain arteriovenous malformation (BAVM), and to analyze whether the rSI and the characteristic of draining veins on silent MRA are associated with hemorrhage presentation. METHODS: Eighty-one draining veins of 46 participants with BAVM (mean age 33.2 ± 16.9 years) who underwent silent MRA and DSA were evaluated retrospectively. The correlation between the rSI of the draining vein on silent MRA and A-V transit time on DSA was examined. The AUC-ROC was obtained to evaluate the performance of the rSI in determining the presence of high-flow A-V shunt. The characteristics of draining veins with the maximum rSI (rSImax) were further compared between the hemorrhagic and non-hemorrhagic untreated BAVM. RESULTS: The rSI of each draining vein on silent MRA was significantly correlated with A-V transit time from DSA (r = -0.81, p < .001). The AUC-ROC was 0.89 for using the rSI to determine the presence of high-flow A-V shunt. A cut-off rSI value of 1.09 yielded a sensitivity of 82.4% and a specificity of 82.8%. The draining vein with rSImax and no ectasia was significantly more observed in the hemorrhagic group (p = 0.045). CONCLUSIONS: The rSI of the draining vein on silent MRA is significantly correlated with A-V transit time on DSA, and it can be used as an indicator of high-flow A-V shunt in BAVM. KEY POINTS: • The signal intensity ratio (rSI) of the draining vein on silent MRA significantly correlated with arteriovenous (A-V) transit time of brain arteriovenous malformation (BAVM) on digital subtraction angiography (DSA). • The area under the receiver operating characteristic curve (AUC) was 0.89 for using the rSI of draining veins to determine high-flow A-V shunt. • Draining veins with maximum rSI and no ectasia were significantly more observed in the hemorrhagic group of BAVM (p = 0.045).

2.
Braz J Med Biol Res ; 54(10): e10891, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34287579

RESUMO

Juniperus communis (JCo) is a well-known traditional Chinese medicinal plant that has been used to treat wounds, fever, swelling, and rheumatism. However, the mechanism underlying the anticancer effect of JCo extract on colorectal cancer (CRC) has not yet been elucidated. This study investigated the anticancer effects of JCo extract in vitro and in vivo as well as the precise molecular mechanisms. Cell viability was evaluated using the MTT assay. Cell cycle distribution was examined by flow cytometry analysis, and cell apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Protein expression was analyzed using western blotting. The in vivo activity of the JCo extract was evaluated using a xenograft BALB/c mouse model. The tumors and organs were examined through hematoxylin-eosin (HE) staining and immunohistochemistry. The results showed that JCo extract exhibited higher cytotoxicity against CRC cells than against normal cells and showed synergistic effects when combined with 5-fluorouracil. JCo extract induced cell cycle arrest at the G0/G1 phase via regulation of p53/p21 and CDK4/cyclin D1 and induced cell apoptosis via the extrinsic (FasL/Fas/caspase-8) and intrinsic (Bax/Bcl-2/caspase-9) apoptotic pathways. In vivo studies revealed that JCo extract suppressed tumor growth through the inhibition of proliferation and induction of apoptosis. In addition, there was no obvious change in body weight or histological morphology of normal organs after treatment. JCo extract suppressed CRC progression by inducing cell cycle arrest and apoptosis in vitro and in vivo, suggesting the potential application of JCo extract in the treatment of CRC.


Assuntos
Adenocarcinoma , Antineoplásicos Fitogênicos , Neoplasias Colorretais , Juniperus , Adenocarcinoma/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacologia
3.
Clin Res Hepatol Gastroenterol ; : 101758, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34303003

RESUMO

BACKGROUND: Whether interferon (IFN)-α therapy is better than nucleos(t)ide analogs (NAs) in the prevention of adverse outcomes, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is still uncertain or controversial. This study aimed to compare the cumulative incidence of adverse outcomes in patients with CHB on IFN-α- and NA-based therapies. METHODS: This was a retrospective study of patients with CHB on antivirals. Patients treated with IFN-α (IFN-α or peginterferon-α) with or without NAs were defined as the IFN-α group, and those only receiving NAs were defined as the NAs group. Propensity score matching (PSM) was used to minimize baseline bias. Cox regression models were performed to select possible factors related to adverse outcomes development. RESULTS: All 1247 patients were divided into the IFN-α (n=877) and NAs (n=370) groups. 26patients (20 and 6 in the NAs and IFN-α groups) developed adverse outcomes (decompensated cirrhosis, liver failure, HCC, liver transplantation and deaths) during a median follow-up of 5.2 years. The cumulative adverse outcomes occurrence at 10 years was significantly lower in the IFN-α group than in the NAs group in all (1.1% vs. 11.9%, P <0.001) and treatment-naïve (1.1% vs. 12.4%, P <0.001) patients. Similar trends were observed after PSM and differentiation of cirrhosis. Multivariate analysis before and after PSM showed that IFN-α-based treatment was independently associated with a lower adverse outcomes incidence (before/after PSM: P=0.001/P=0.002). HCC risk stratification analyses revealed that the superiority of IFN-α in preventing HCC was more significant in patients with high-risk HCC. CONCLUSIONS: IFN-α-based therapy was superior to NAs in preventing adverse outcomes in patients with CHB regardless of cirrhosis, and in reducing HCC in those with a high risk of HCC.

4.
Laryngoscope ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34287919

RESUMO

OBJECTIVES: Congenital tracheal stenosis (CTS) is a rare but life-threatening condition in children. At present, slide tracheoplasty has been advocated as the preferred technique for most cases of CTS. However, the morbidity and mortality subsequent to slide tracheoplasty need further elaboration. Therefore, a meta-analysis was performed on the outcomes of slide tracheoplasty in children with CTS. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases, including PubMed, Embase, and Cochrane Library CENTRAL, were systematically searched for the period from January 1990 to March 2021 for literature that reported clinical outcomes of slide tracheoplasty for children with CTS. Meta-regression and subgroup analyses were performed to determine the risk factors for in-hospital mortality and airway reinterventions. RESULTS: A total of 25 studies involving 577 patients were included. For children with CTS, in-hospital and overall mortality after slide tracheoplasty was 6.1% (95% CI = 4.2%-8.0%) and 9.7% (95% CI = 7.3%-12.1%), respectively. The incidence of airway reinterventions was 23.0% (95% CI = 15.6%-30.5%). The length of postoperative ventilation and hospital stay was 6.8 days (95% CI = 5.1-8.4 days) and 19.2 days (95% CI = 15.8-22.7 days), respectively. Postoperative complications occurred in 46.6% (95% CI = 35.8%-57.4%) of all patients. Meta-regression analysis showed that a higher proportion of the recently published studies reported significantly better in-hospital survival (coefficient -0.011, P = .021). CONCLUSIONS: In conclusion, in-hospital mortality after slide tracheoplasty is 6.1%, and the incidence of airway reinterventions is 23.0%. In-hospital mortality after slide tracheoplasty has decreased chronologically. LEVEL OF EVIDENCE: NA Laryngoscope, 2021.

5.
Inflamm Res ; 70(8): 891-902, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34223915

RESUMO

OBJECTIVE: Regulatory T cells (Tregs) and T helper (Th) 17 cells are two subsets of CD4 + T cells with opposite effects which play a crucial role in the pathogenesis of lung injury. In this study, we aim to investigate the protective effect of Pseudomonas aeruginosa outer membrane vesicles (OMVs) preconditioning on lung ischemia-reperfusion (I/R) injury and potential mechanisms. METHODS: Pathogen-free C57BL/6 mice were randomly divided into four groups: control, Control + OMVs, I/R and I/R + OMVs groups. Bronchoalveolar lavage fluid (BALF), serum, and lung tissues were collected and analyzed for pathophysiology and immune mechanism. RESULTS: OMVs not only attenuated tissue injury and respiratory physiologic function but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration. The numbers of total cells, macrophages, neutrophils, and lymphocytes were markedly decreased in the I/R mice following OMVs preconditioning. OMVs also decreased inflammatory cytokines associated with CD4 + T cells in both BALF and serum. In addition, the level of Tregs and its transcription factor forkhead box P3 (Foxp3) were significantly increased, while the level of Th17 cells and its transcription factor retinoid-related orphan receptor γ (RORγt) were significantly decreased following OMVs preconditioning. In the process of exploring the underlying protection mechanisms of OMVs, we found that OMVs preconditioning significantly reduced protein expression of Toll-like receptor 4 (TLR4), which in turn not only inactivated myeloid differentiation factor 88 (MyD88) and Phosphorylated nuclear factor kappa B (p-NF-κB), but also simultaneously increased the levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). CONCLUSIONS: These results suggest that OMVs preconditioning may ameliorate lung I/R injury by regulating the balance of Tregs and Th17 cells through Tim-3 and TLR4/NF-κB pathway.

6.
Comput Biol Med ; 135: 104634, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34256255

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused worldwide pandemic and is responsible for millions of worldwide deaths due to -a respiratory disease known as COVID-19. In the search for a cure of COVID-19, drug repurposing is a fast and cost-effective approach to identify anti-COVID-19 drugs from existing drugs. The receptor binding domain (RBD) of the SARS-CoV-2 spike protein has been a main target for drug designs to block spike protein binding to ACE2 proteins. In this study, we probed the conformational plasticity of the RBD using long molecular dynamics (MD) simulations, from which, representative conformations were identified using clustering analysis. Three simulated conformations and the original crystal structure were used to screen FDA approved drugs (2466 drugs) against the predicted binding site at the ACE2-RBD interface, leading to 18 drugs with top docking scores. Notably, 16 out of the 18 drugs were obtained from the simulated conformations, while the crystal structure suggests poor binding. The binding stability of the 18 drugs were further investigated using MD simulations. Encouragingly, 6 drugs exhibited stable binding with RBD at the ACE2-RBD interface and 3 of them (gonadorelin, fondaparinux and atorvastatin) showed significantly enhanced binding after the MD simulations. Our study shows that flexibility modeling of SARS-CoV-2 RBD using MD simulation is of great help in identifying novel agents which might block the interaction between human ACE2 and the SARS-CoV-2 RBD for inhibiting the virus infection.

7.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208566

RESUMO

Regarding the increased incidence and high mortality rate of malignant melanoma, practical early-detection methods are essential to improve patients' clinical outcomes. In this study, we successfully prepared novel picolinamide-benzamide (18F-FPABZA) and nicotinamide-benzamide (18F-FNABZA) conjugates and determined their biological characteristics. The radiochemical yields of 18F-FPABZA and 18F-FNABZA were 26 ± 5% and 1 ± 0.5%, respectively. 18F-FPABZA was more lipophilic (log P = 1.48) than 18F-FNABZA (log P = 0.68). The cellular uptake of 18F-FPABZA in melanotic B16F10 cells was relatively higher than that of 18F-FNABZA at 15 min post-incubation. However, both radiotracers did not retain in amelanotic A375 cells. The tumor-to-muscle ratios of 18F-FPABZA-injected B16F10 tumor-bearing mice increased from 7.6 ± 0.4 at 15 min post-injection (p.i.) to 27.5 ± 16.6 at 3 h p.i., while those administered with 18F-FNABZA did not show a similarly dramatic increase throughout the experimental period. The results obtained from biodistribution studies were consistent with those derived from microPET imaging. This study demonstrated that 18F-FPABZA is a promising melanin-targeting positron emission tomography (PET) probe for melanotic melanoma.


Assuntos
Radioisótopos de Flúor , Melanoma Experimental/diagnóstico por imagem , Niacinamida , Ácidos Picolínicos , Compostos Radiofarmacêuticos , Animais , Linhagem Celular Tumoral , Radioisótopos de Flúor/química , Melaninas/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Niacinamida/química , Ácidos Picolínicos/química , Tomografia por Emissão de Pósitrons , Ligação Proteica , Compostos Radiofarmacêuticos/química , Distribuição Tecidual
8.
Medicine (Baltimore) ; 100(27): e26536, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232191

RESUMO

BACKGROUND: This meta-analysis aimed to synthesize randomized controlled trials to evaluate the effects of enhanced external counterpulsation (EECP) on exercise capacity and quality of life in patients with chronic heart failure (CHF). METHODS: Both English and Chinese databases were searched from their inception to June 30, 2020 (PubMed, EMBASE, Cochrane Library, CINAHL (EBSCO), Web of Science for English publications and Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Data for Chinese publication). Titles, abstracts, and full-text articles were screened against study inclusion criteria: randomized controlled trials studying EECP intervention for patients with CHF. The meta-analysis was conducted with Revman 5.3 or STATA 16.0. RESULTS: Eight randomized controlled trials were included. EECP induced significant improvement in 6-min walking distance (WMD=84.79 m; 95% CI, 47.64 to 121.95; P < .00001). Moreover, EECP was beneficial for left ventricular ejection fraction (SMD = 0.64; 95% CI,0.29 to 1.00; P = .0004), and N-terminal pro brain natriuretic peptide (SMD = -0.61; 95%CI, -1.20 to -0.01; P = 0.04).However, compared with the control groups, EECP did not significantly reduce the Minnesota Living with Heart Failure Questionnaire scores(WMD, -9.28; 95% CI, -19.30 to 0.75; P = 0.07). CONCLUSIONS: Despite heterogeneity and risk of bias, this meta-analysis confirms that EECP can improve exercise capacity in CHF patients, especially the elderly. However, the evidence that EECP improves the quality of life in patients with CHF is still insufficient. More and larger well-designed randomized controlled trials are still warranted. REGISTRATION INFORMATION: PROSPERO registration no. CRD 42020188848.


Assuntos
Contrapulsação/métodos , Insuficiência Cardíaca/terapia , Qualidade de Vida , Volume Sistólico/fisiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos
9.
Asian J Anesthesiol ; : 1-6, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266229

RESUMO

BACKGROUND: General anesthesia or sedation is commonly required for pediatric patients undergoing magnetic resonance imaging (MRI) scans, and airway management during the procedure is the highest concern for anesthesiologists owing to the limited access to the patient in the MRI unit. The use of supraglottic airway devices (SADs) has recently become more popular than endotracheal tubes; however, the feasibility of using SADs for children in MRI suites was reported only in a few studies that involved healthy patients. METHODS: We present a successful case series of 30 pediatric patients, and the majority are high-risk patients, including patients with aromatic L-amino acid decarboxylase (AADC) deficiency, mitochondrial disease, and tuberous sclerosis, using either i-gel or laryngeal masks for airway maintenance during MRI examination. RESULTS: A total of 38 MRI exams were conducted; the patients' median age was 4 (range 1.6-17.0 years), and the mean examination time was 50.87 minutes. No patient experienced oxygen desaturation, and only 1 patient with AADC deficiency had an episode of hypotension. The MRI scans were completed without interruption with an adequate image quality according to a specialized radiologist. CONCLUSION: From the clinical point of view, this case series demonstrated a broader application of SADs for airway maintenance during MRI scans for pediatric patients with a high risk during anesthesia rather than only for a healthy patient population.

10.
Anal Chem ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241990

RESUMO

Four-dimensional printing (4DP) technologies can extend the functionality and applicability of manufactured analytical devices through employing stimuli-responsive materials. In this study, we used a photocurable resin of stimuli-responsive shape-memory polymers and digital light processing three-dimensional printing (3DP) to fabricate a smart sample pretreatment device featuring a solid-phase extraction (SPE) column and a temperature-controlled flow-actuated valve. Through manipulation of the temperatures and flow rates of the sample, eluent, and rinsing streams, we used this 4D-printed SPE device to extract Mn, Co, Ni, Cu, Zn, Cd, and Pb ions from high-salt content samples and remove the sample matrix prior to their determination by inductively coupled plasma mass spectrometry. After optimizing the valve design and operation and the analytical scheme, this device displayed competitive analytical performance-the method detection limits (MDLs) ranged from 0.7 to 22.1 ng L-1 for these metal ions (the MDLs ranged from 0.5 to 18.8 ng L-1 when validating the same printed SPE column using an online automatic system equipped with electric switching valves). Furthermore, we performed analyses of these metal ions in three reference materials (CASS-4, 1643f, and 2670a) and spike analyses of collected samples (seawater, ground water, river water, and human urine) to confirm the reliability and applicability of this analytical method. For the first time, 4DP has been used to fabricate a multi-functional, stimuli-responsive sample pretreatment device displaying analytical performance equal to that of a commercial apparatus. This novel approach builds upon the functionality and diversity of 3DP-enabling devices with the goal of developing more efficient analytical schemes.

11.
Inorg Chem ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236845

RESUMO

The synthesis, structural characteristics, and photophysical properties of luminescent Cu-rich bimetallic superatomic clusters [Au@Cu12(S2CNnPr2)6(C≡CPh)4]+ (1a+), [Au@Cu12{S2P(OR)2}6(C≡CPh)4]+ (2+), (2a+ = iPr; 2b+ = nPr), [Au@Cu12{S2P(C2H4Ph)2}6(C≡CPh)4]+ (2c+), and [Ag@Cu12{S2P(OnPr)2}6(C≡CPh)4]+ (3+) were studied. Compositionally uniform clusters 1+-3+ were isolated from the reaction of dithiolato-stabilized, polyhydrido copper clusters with phenylacetylene in the presence of heterometal salts. By using X-ray diffraction, the structures of 1a+, 2a+, 2b+, and 3+ were able to be determined. ESI-mass spectrometry and elemental analysis confirmed their compositions and purity. The structural characteristics of these clusters are similar with respect to displaying gold (or silver)-centered Cu12 cuboctahedra surrounded by six dithiocarbamate/dithiophosph(in)ate and four alkynyl ligands. The doping of Au and Ag atoms into the polyhydrido copper nanoclusters significantly enhances their PL quantum yields from Ag@Cu12 (0.58%) to Au@Cu12 (55%) at ambient temperature in solution. In addition, the electrochemical properties of the new alloys were investigated by cyclic voltammetry.

12.
Nat Mater ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239084

RESUMO

The antagonism between strength and resistance to hydrogen embrittlement in metallic materials is an intrinsic obstacle to the design of lightweight yet reliable structural components operated in hydrogen-containing environments. Economical and scalable microstructural solutions to this challenge must be found. Here, we introduce a counterintuitive strategy to exploit the typically undesired chemical heterogeneity within the material's microstructure that enables local enhancement of crack resistance and local hydrogen trapping. We use this approach in a manganese-containing high-strength steel and produce a high dispersion of manganese-rich zones within the microstructure. These solute-rich buffer regions allow for local micro-tuning of the phase stability, arresting hydrogen-induced microcracks and thus interrupting the percolation of hydrogen-assisted damage. This results in a superior hydrogen embrittlement resistance (better by a factor of two) without sacrificing the material's strength and ductility. The strategy of exploiting chemical heterogeneities, rather than avoiding them, broadens the horizon for microstructure engineering via advanced thermomechanical processing.

13.
J Chem Phys ; 154(23): 234303, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34241253

RESUMO

Molecular electronic or vibrational states can be superimposed temporarily in an extremely short laser pulse, and the superposition-state transients formed therein receive much attention, owing to the extensive interest in molecular fundamentals and the potential applications in quantum information processing. Using the crossed-beam ion velocity map imaging technique, we disentangle two distinctly different pathways leading to the forward-scattered N2 + yields in the large impact-parameter charge transfer from low-energy Ar+ to N2. Besides the ground-state (X2Σg +) N2 + produced in the energy-resonant charge transfer, a few slower N2 + ions are proposed to be in the superpositions of the X2Σg +-A2Πu and A2Πu-B2Σu + states on the basis of the accidental degeneracy or energetic closeness of the vibrational states around the X2Σg +-A2Πu and A2Πu-B2Σu + crossings in the non-Franck-Condon region. This finding potentially shows a brand-new way to prepare the superposition-state molecular ion.

14.
J Phys Chem Lett ; : 7127-7133, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296886

RESUMO

Long-distance charge-dipole attraction between atomic ion and randomly oriented polar molecule potentially makes the molecular orientation, which profoundly influences the products' kinetics of collisional reaction. Using the three-dimensional ion velocity map imaging technique, here we report a collision-energy dependent stereodynamics of dissociative charge exchange reaction Ar+ + CO → Ar + O + C+ in a range of 7.46-9.97 eV. At the lowest collision energy, the most C+ products are forward-scattered and are along the collision axis and are attributed to three different dissociation channels including the predominant one experiencing the rotating intermediate ArC+. At the high collision energies, the remarkably diffusive distribution of C+ arises from the prompt dissociation of the rebounded CO+. The different dynamic processes arising from the nearly collinear collision are elaborated explicitly on the basis of the data analyses using the Doppler kinetics models.

15.
J Glob Health ; 11: 05019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326999

RESUMO

Background: Scientists have demonstrated the efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 in randomized controlled trials. However, the extent to which reductions in COVID-19 case fatality ratio (CFR) are attributable to mass vaccination in the real world remains unclear. This study evaluated the association of COVID-19 vaccine coverage with CFR on a global scale. Methods: The sample was a longitudinal data set of 90 countries over 25 weeks, from the first week of November 2020 to the third week of April 2021. CFR was measured in deaths per 100 COVID-19 confirmed cases; vaccine coverage was defined as the number of people who received at least one vaccine dose per 10 people in the total population. Data were retrieved from open-access databases, including Our World in Data and the Oxford COVID-19 Government Response Tracker. A country-level random effects model was used; a comprehensive set of variables for country characteristics and nonpharmaceutical interventions were included. Results: A 10% increase in vaccine coverage was associated with a 7.6% reduction in the CFR (95% confidence interval (CI = -12.6 to -2.7%, P = 0.002). This association was stronger in countries with more effective governments (-8.3%; 95% CI = -13.6 to -3.1%, P = 0.002) and higher transport infrastructure quality (-8.1%; 95% CI = -13.3 to -2.9%, P = 0.002). Moreover, the vaccine coverage was associated with a reduced CFR in a dose-dependent manner. When vaccine coverage achieved 0.8 to 1.6, 1.6 to 3.2 and ≥3.2 per 10 people, the CFR reduced by 12.7% (95 CI = -21.8 to -3.6%, P = 0.006), 21.2% (95 CI = -33.9 to -8.5%, P = 0.001) and 31.3% (95 CI = -51.5 to -11.0%, P = 0.002), respectively as compared with no vaccination. Conclusions: Our results provide supporting evidence that vaccination is critical to preventing deaths among infected people. Vaccination programmes have yielded significant health benefits in certain countries. However, globally, a large gap remains between observed and achievable fatality reductions. Continuous improvement in vaccine coverage will be critical to transforming efficacious vaccines into desired health outcomes.

16.
Environ Toxicol Pharmacol ; 87: 103714, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34302971

RESUMO

Persistent ketamine use causes susceptibility to addiction and bladder toxicity. We examined the association of lower urinary tract symptoms and levels of Nectin-4, a member of the cell adhesion molecules that is essential for maintaining the urothelium barrier in chronic ketamine abusers. We measured the plasma levels of Nectin-4 in 88 patients with ketamine dependence and 69 controls. Patients with ketamine dependence were assessed for ketamine use variables, psychological symptoms, and lower urinary tract symptoms. We found Nectin-4 levels were increased in ketamine-dependent patients compared to the controls (p < 0.0001). Patients with urinary tract symptoms exhibited lower Nectin-4 levels than those without (p = 0.021). Our results suggest an up-regulation of Nectin-4 following chronic and heavy ketamine use. Patients with ketamine dependence with a compromised upregulation of Nectin-4 are likely to have more severe urinary tract symptoms. The mechanisms underlying the involvement of Nectin-4 in ketamine addiction and bladder toxicity warrant future investigation.

17.
BMC Womens Health ; 21(1): 276, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325677

RESUMO

BACKGROUND: Gynecologic cancers are among the most prevalent malignancies in China. Cervical and uterine cancer respectively account for the sixth and eighth highest incidence of cancer among Chinese women. Abdominal surgery is one of the important treatment methods for gynecological tumors. However, the tumor- and surgery-related symptom burden are not well studied owing to a lack of a standardized and validated assessment tool in the Chinese population. The study aimed to translate and validate the MD Anderson Symptom Inventory for measuring perioperative symptom burden in gynecologic cancer patients (MDASI-PeriOp-GYN) and examine the utility of the Chinese version of MDASI-PeriOp-GYN. METHODS: The MDASI-PeriOp-GYN was translated in a stepwise manner. First, two native speakers independently translated the 9 PeriOp-GYN symptom items. Then the nine items were translated back into English by two different bilingual translators. After discussion and revision, the four translators reached an agreement. Finally, the finalized Chinese version was administered to women with three common gynecologic cancer types (cervical, ovarian, and endometrial cancers) recruited from the gynecological oncology department of Sichuan Cancer Hospital & Institute between July and October 2019. The reliability and validity of the translated version were assessed. RESULTS: Overall, 324 women with gynecologic cancers were enrolled. Cronbach's α values were 0.826 and 0.735 for the symptom severity and interference scales, respectively. Test-retest reliability values were 0.885, 0.873, and 0.914 for symptom severity, PeriOp-GYN, and interference scales. Significant correlations were found between the MDASI-PeriOp-GYN-C and EORTC QLQ-C30 along with the QLQ-OV28 module (- 0.608-0.871, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by time intervals, surgery type, and functional status (all P < 0.01). CONCLUSIONS: The MDASI-PeriOp-GYN-C is a valid and reliable tool for measuring symptoms in Chinese patients undergoing surgery for gynecologic cancers. The tool could be used in clinical practice and clinical trials to instantly gather patients' health and quality of life data.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34275915

RESUMO

BACKGROUND: Motor and cognitive decline as part of the normal aging process is linked to alterations in synaptic plasticity and reduction of adult neurogenesis in the dorsal striatum. Neuroinflammation, particularly in the form of microglial activation, is suggested to contribute to these age-associated changes. OBJECTIVE AND METHODS: To explore the molecular basis of alterations in striatal function during aging we analyzed RNA-Seq data for 117 postmortem human dorsal caudate samples and 97 putamen samples acquired through GTEx. RESULTS: Increased expression of neuroinflammatory transcripts including TREM2, MHC II molecules HLA-DMB, HLA-DQA2, HLA-DPA1, HLA-DPB1, HLA-DMA and HLA-DRA, complement genes C1QA, C1QB, CIQC and C3AR1, and MHCI molecules HLA-B and HLA-F was identified. We also identified down-regulation of transcripts involved in neurogenesis, synaptogenesis, and synaptic pruning, including DCX, CX3CL1, and CD200, and the canonical WNTs WNT7A, WNT7B, and WNT8A. The canonical WNT signaling pathway has previously been shown to mediate adult neurogenesis and synapse formation and growth. Recent findings also highlight the link between WNT/ß-catenin signaling and inflammation pathways. CONCLUSIONS: These findings suggest that age-dependent attenuation of canonical WNT signaling plays a pivotal role in regulating striatal plasticity during aging. Dysregulation of WNT/ß-catenin signaling via astrocyte-microglial interactions is suggested to be a novel mechanism that drives the decline of striatal neurogenesis and altered synaptic connectivity and plasticity, leading to a subsequent decrease in motor and cognitive performance with age. These findings may aid in the development of therapies targeting WNT/ß-catenin signaling to combat cognitive and motor impairments associated with aging.

19.
Inorg Chem ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278784

RESUMO

Three thiocyanate-free cycloruthenated complexes, DUY24-O, DUY24, and DUY24-Se containing furan, thiophene, and selenophene, respectively, as a part of the cycloruthenated ring, were designed to reveal the function of the chalcogen atom on the physicochemical and photovoltaic performance of the cycloruthenated sensitizers applied in dye-sensitized solar cells (DSCs). The three sensitizers have a similar molecular size; therefore, the effect of molecular dimensions on their photovoltaic performance can be negligible. NMR data, electron-donating resonance effects, optical properties, and the energy levels of the frontier orbitals reveal that the physical/photovoltaic properties of the three sensitizers were affected significantly by the chalcogen atom on the cyclometalated chalcogenophene ring. The λmax (both in ethanol and adsorbed on TiO2), frontier orbital level, and dye loading of thiophene- and selenophene-containing dyes are very close. Nevertheless, DUY24-Se has a higher molar absorption coefficient compared to DUY24; therefore, the DSC based on DUY24-Se has higher efficiency (8.4% under AM1.5 G one-sun and 26% under T5-light at ca. 6000 lux) than that sensitized with the DUY24 dye. These efficiencies are also higher than those (7.9 and 21.6%, respectively) of the cell dyed with N719, fabricated using the same conditions. The better performance of the device sensitized with DUY24-Se compared to DUY24-based cells suggests that selenophene is as good as (or even better than) thiophene to be a part of the cyclometalated ring for thiocyanate-free cycloruthenated sensitizers applied in DSCs. Furan-containing DUY24-O has much worse photovoltaic performance compared to the other two dyes. This is not only because DUY24-O has the shortest λmax, the lowest molar absorption coefficient, and the highest HOMO level but also the lowest dye loading (because of the strong interaction between the oxygen in furan and TiO2, the array of DUY24-O occupies more surface when adsorbed on TiO2) and the fastest charge recombination. The physicochemical and photovoltaic properties as well as the adsorption behavior of the dye on the TiO2 anode for the cycloruthenated sensitizers affected significantly by the chalcogen atom of the chalcogenophene on the cyclometalated ring provide a new strategy to design high-efficiency NCS-free cyclometalated sensitizers for DSCs.

20.
J Neurogenet ; : 1-11, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34278939

RESUMO

Hypersynchronous neural activity is a characteristic feature of seizures. Although many Drosophila mutants of epilepsy-related genes display clear behavioral spasms and motor unit hyperexcitability, field potential measurements of aberrant hypersynchronous activity across brain regions during seizures have yet to be described. Here, we report a straightforward method to observe local field potentials (LFPs) from the Drosophila brain to monitor ensemble neural activity during seizures in behaving tethered flies. High frequency stimulation across the brain reliably triggers a stereotypic sequence of electroconvulsive seizure (ECS) spike discharges readily detectable in the dorsal longitudinal muscle (DLM) and coupled with behavioral spasms. During seizure episodes, the LFP signal displayed characteristic large-amplitude oscillations with a stereotypic temporal correlation to DLM flight muscle spiking. ECS-related LFP events were clearly distinct from rest- and flight-associated LFP patterns. We further characterized the LFP activity during different types of seizures originating from genetic and pharmacological manipulations. In the 'bang-sensitive' sodium channel mutant bangsenseless (bss), the LFP pattern was prolonged, and the temporal correlation between LFP oscillations and DLM discharges was altered. Following administration of the pro-convulsant GABAA blocker picrotoxin, we uncovered a qualitatively different LFP activity pattern, which consisted of a slow (1-Hz), repetitive, waveform, closely coupled with DLM bursting and behavioral spasms. Our approach to record brain LFPs presents an initial framework for electrophysiological analysis of the complex brain-wide activity patterns in the large collection of Drosophila excitability mutants.

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