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1.
Artigo em Inglês | MEDLINE | ID: mdl-32621959

RESUMO

Functional dysconnectivity has been widely reported in bipolar disorder during depressive episodes (BDD). However, the frequency-specific alterations of functional connectivity (FC) in BDD remain poorly understood. To address this issue, the FC patterns across slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) bands were computed using resting-state functional magnetic resonance imaging data from 37 BDD patients and 56 healthy controls (HCs). Short-range (local) FC density (lfcd) and long-range FC density (lrfcd) were calculated, and two-way analysis of variance was performed to ascertain the main effect of diagnosis and interaction effects between diagnosis and frequency. The BDD patients showed increased lfcd in the midline cerebelum. Meanwhile, the BDD patients showed increased lrfcd in the left supplementary motor cortex and right striatum and decreased lrfcd in the bilateral inferior temporal gyrus and left angular gyrus (AG) compared with the HCs. A significant frequency-by-diagnosis interaction was observed. In the slow-4 band, the BDD patients showed increased lfcd in the left pre-/postcentral gyrus and left fusiform gyrus (FG) and increased lrfcd in the left lingual gyrus (LG). In the slow-5 band, the BDD patients showed decreased lrfcd in the left LG. Moreover, the increased lfcd in the left FG in the slow-4 band was correlated with clinical progression and decreased lrfcd in the left AG was correlated with depressive severity. These results suggest that the presence of aberrant communication in the default mode network, sensory network, and subcortical and limbic modulating regions (striatum and midline cerebelum), which may offer a new framework for the understanding of the pathophysiological mechanisms of BDD.

2.
J Adv Nurs ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009847

RESUMO

AIMS: To assess the effects of upright positions on maternal outcomes for women without epidural analgesia in comparison with recumbent positions during the second stage of labour. BACKGROUND: Upright positions have many physiological advantages. The underlying benefits and risks of upright positions during the second stage of labour have been reported in many studies but the results are divergent. DESIGN: A meta-analysis of randomized controlled trials. DATA SOURCES: The Cochrane Library, PubMed, Embase, CINAHL and ProQuest databases were systematically searched from inception to 17 June 2019. REVIEW METHODS: We conducted the quality appraisal using the Cochrane Collaboration's tool and performed meta-analyses using the Review Manager 5.3 software. The primary outcomes were instrumental vaginal delivery and the duration of the second stage of labour. RESULTS: Overall, 12 studies including 4,314 women were included. Upright positions significantly decreased the rate of instrumental vaginal delivery (risk ratio [RR] = 0.74, 95% CI 0.59-0.93), shortened the active pushing phase (mean difference [MD] = -8.16 min, 95% CI -16.29 to -0.02), decreased the rate of severe perineal trauma (RR = 0.35, 95% CI 0.14-0.87) and episiotomy (RR = 0.52, 95% CI 0.29-0.92), but significantly increased the rate of second-degree perineal trauma (RR = 1.45, 95% CI 1.10-1.90). However, there was no significant difference in the duration of the second stage of labour or postpartum haemorrhage. CONCLUSIONS: Upright positions are beneficial for improving maternal outcomes. Several results should be considered with caution. Researchers need to clarify the definition of upright positions and conduct large, robust studies in the future to provide stronger evidence. IMPACT: This meta-analysis explores a crucial issue in intrapartum care and clarifies the benefits and possible risks of upright positions in the second stage of labour. Midwives and obstetricians are encouraged to apply upright positions depending on women's preferences and labour progress but should take measures to prevent perineal trauma.

3.
Biomarkers ; : 1-23, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025829

RESUMO

Objective: To investigate the associations between anti-Müllerian hormone (AMH) and bone mineral density (BMD) induced by ovarian insufficiency in premenopausal women.Methods: Subjects were consecutively enrolled from January 2015 to December 2018. Dual energy X-ray absorptiometry examination was set as the gold standard, with T-scores less than -2.5/-1 as thresholds for the definition of osteoporosis/osteopenia.Results: A total of 87 subjects were included in the low BMD group, and 39 subjects were included in the control group. Serum AMH levels were decreased significantly in the low BMD group (p < 0.05) with a negative correlation between AMH and age. Strong positive correlations between AMH and BMD/T-score existed in all subjects and subjects with low BMD, and remained even after age adjustment. An exploratory multivariate regression model indicated that age and AMH remained predictive and might be independent risk factors with adjusted odds ratios of 0.9 (p = 0.009) and 36 (p < 0.001), respectively. The receiver operating characteristic curve analysis estimated that the sensitivity and specificity were 78.2% and 76.9%, respectively, for identifying low BMD subjects from controls when the cutoff value for AMH was set to 0.800 ng/mL.Conclusions: Serum AMH levels are associated with low BMD in premenopausal women with suspected ovarian insufficiency.

4.
Front Immunol ; 11: 2001, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013854

RESUMO

Background: X-linked agammaglobulinemia (XLA) is caused by a mutation of the Bruton's tyrosine kinase (BTK) gene and is the most common genetic mutation in patients with congenital agammaglobulinemia. The aim of this study was to analyze the clinical features, genetic defects, and/or BTK expression in patients suspected of having XLA who were referred from the Taiwan Foundation of Rare Disorders (TFRD). Methods: Patients with recurrent bacterial infections in the first 2 years of life, serum IgG/A/M below 2 standard deviations of the normal range, and ≦2% CD19+B cells were enrolled during the period of 2004-2019. The frequency of infections, pathogens, B-lymphocyte subsets, and family pedigree were recorded. Peripheral blood samples were sent to our institute for BTK expression and genetic analysis. Results: Nineteen (from 16 families) out of 29 patients had BTK mutations, including 7 missense mutations, 7 splicing mutations, 1 nonsense mutation, 2 huge deletions, and 2 nucleotide deletions. Six novel mutations were detected: c.504G>T [p.K168N], c.895-2A>G [p.Del K290 fs 23*], c.910T>G [p.F304V], c.1132T>C [p.T334H], c.1562A>T [p.D521V], and c.1957delG [Del p.D653 fs plus 45 a.a.]. All patients with BTK mutations had obviously decreased BTK expressions. Pseudomonas sepsis developed in 14 patients and led to both Shanghai fever and recurrent hemophagocytic lymphohistiocytosis (HLH). Recurrent sinopulmonary infections and bronchiectasis occurred in 11 patients. One patient died of pseudomonas sepsis and another died of hepatocellular carcinoma before receiving optimal treatment. Two patients with contiguous gene deletion syndrome (CGS) encompassing the TIMM8A/DDP1 gene presented with early-onset progressive post-lingual sensorineural Deafness, gradual Dystonia, and Optic Neuronopathy syndrome (DDON) or Mohr-Tranebjaerg syndrome (MTS). Conclusion: Pseudomonas sepsis was more common (74%) than recurrent sinopulmonary infections in Taiwanese XLA patients, and related to Shanghai fever and recurrent HLH, both of which were prevented by regular immunoglobulin infusions. Approximately 10% of patients belonged to CGS involving the TIMM8A/DDP1 gene and presented with the DDON/MTS phenotype in need of aggressive psychomotor therapy.

5.
Infect Genet Evol ; : 104582, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33017689

RESUMO

PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin, a pore-forming toxin, is a common cause of necrotizing pneumonia. However, the early pulmonary inflammatory response following PVL(+) MRSA infection is unknown. The purpose of this study was to use a murine model to determine the effect of PVL(+) MRSA on lung tissues and the expression of cytokines and JAK and STAT mRNA and protein. METHODS: Mice were randomly divided into 3 groups and intra-nasally treated with PBS (control group), recombinant PVL (rPVL group), and PVL(+) MRSA (PVL group). At 24 and 48 h after inoculation, bronchoalveolar lavage fluid (BALF) was tested for cytokine levels, and lung tissues were tested for JAK and STAT mRNA and protein expression, and examined after hematoxylin and eosin staining. RESULTS: Mice infected with the PVL(+) strain became ill, characterized by impaired mobility, hunched posture, ruffled fur, and labored breathing. Lung tissue exhibited tissue necrosis and hemorrhage. BALF levels of IL-8, TNF-α, IFN-γ, IL-12, sICAM-1, and sVCAM-1 were increased in the rPVL or PVL groups, while levels of IL-10 and IL-4 levels were similar among the groups. JAK1 and STAT1 mRNA expression and protein levels were increased in lung tissue from mice infected with PVL(+) MRSA and rPVL. CONCLUSIONS: PVL is a significant S. aureus virulence factor, and upregulates the expression of proinflammatory cytokines but does not affect the expression of anti-inflammatory cytokines. The effect of PVL may be due to JAK/STAT pathway activation. Blockade of the JAK/STAT pathway may decrease the severity of PVL(+) MRSA pneumonia.

6.
Adv Mater ; : e2003708, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015921

RESUMO

The development of nanozymes has made active impact in diagnosis and therapeutics. However, understanding of the full effects of these nanozymes on biochemical pathways and metabolic homeostasis remains elusive. Here, it is found that iron oxide nanoparticles (Fe3 O4 NPs), a type of well-established nanozyme, can locally regulate the energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) via their peroxidase-like activity in the acidic lysosomal compartment, thereby promoting glucose metabolism and insulin response. Fe3 O4 NPs induce AMPK activation and enhance glucose uptake in a variety of metabolically active cells as well as in insulin resistant cell models. Dietary Fe3 O4 NPs display therapeutic effects on hyperglycemia and hyperinsulinemia in Drosophila models of diabetes induced by genetic manipulation or high-sugar diet. More importantly, intraperitoneal administration of Fe3 O4 NPs stimulates AMPK activities in metabolic tissues, reduces blood glucose levels, and improves glucose tolerance and insulin sensitivity in diabetic ob/ob mice. The study reveals intrinsic organelle-specific properties of Fe3 O4 NPs in AMPK activation, glycemic control, and insulin-resistance improvement, suggesting their potential efficacy in diabetes care.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33046245

RESUMO

BACKGROUND: The underlying mechanism of viral infection as a risk factor for Parkinson's disease (PD), the second most common neurodegenerative disease, remains unclear. OBJECTIVE: We used Mac-1-/- and gp91phox-/- transgene animal models to investigate the mechanisms by which poly I:C, a mimic of virus double-stranded RNA, induces PD neurodegeneration. METHOD: Poly I:C was stereotaxically injected into the substantia nigra (SN) of wild-type (WT), Mac-1-knockout (Mac-1-/-) and gp91 phox-knockout (gp91 phox-/-) mice (10 µg/µl), and nigral dopaminergic neurodegeneration, α-synuclein accumulation and neuroinflammation were evaluated. RESULT: Dopaminergic neurons in the nigra and striatum were markedly reduced in WT mice after administration of poly I:C together with abundant microglial activation in the SN, and the expression of α-synuclein was also elevated. However, these pathological changes were greatly dampened in Mac-1-/- and gp91 phox-/- mice. CONCLUSIONS: Our findings demonstrated that viral infection could result in the activation of microglia as well as NADPH oxidase, which may lead to neuron loss and the development of Parkinson's-like symptoms. Mac-1 is a key receptor during this process.

9.
Cancers (Basel) ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066043

RESUMO

New approaches to target MYC include the stabilization of a guanine-rich, G-quadruplex (G4) tertiary DNA structure in the NHE III region of its promoter. Recent screening of a small molecule microarray platform identified a benzofuran, D089, that can stabilize the MYC G4 and inhibit its transcription. D089 induced both dose- and time-dependent multiple myeloma cell death mediated by endoplasmic reticulum induced stress. Unexpectedly, we uncovered two mechanisms of cell death: cellular senescence, as evidenced by increased levels of p16, p21 and γ-H2AX proteins and a caspase 3-independent mechanism consistent with pyroptosis. Cells treated with D089 exhibited high levels of the cleaved form of initiator caspase 8; but failed to show cleavage of executioner caspase 3, a classical apoptotic marker. Cotreatment with the a pan-caspase inhibitor Q-VD-OPh did not affect the cytotoxic effect of D089. In contrast, cleaved caspase 1, an inflammatory caspase downstream of caspases 8/9, was increased by D089 treatment. Cells treated with D089 in addition to either a caspase 1 inhibitor or siRNA-caspase 1 showed increased IC50 values, indicating a contribution of cleaved caspase 1 to cell death. Downstream effects of caspase 1 activation after drug treatment included increases in IL1B, gasdermin D cleavage, and HMGB1 translocation from the nucleus to the cytoplasm. Drug treated cells underwent a 'ballooning' morphology characteristic of pyroptosis, rather than 'blebbing' typically associated with apoptosis. ASC specks colocalized with NLRP3 in proximity ligation assays after drug treatment, indicating inflammasome activation and further confirming pyroptosis as a contributor to cell death. Thus, the small molecule MYC G4 stabilizer, D089, provides a new tool compound for studying pyroptosis. These studies suggest that inducing both tumor senescence and pyroptosis may have therapeutic potential for cancer treatment.

10.
Curr Med Res Opin ; : 1, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066709

RESUMO

AIMS: To explore whether newly diagnosed Candida infection with risk of developing ankylosing spondylitis (AS). Methods and materials: We investigated 61,550 patients with newly diagnosed Candida infection between 1997 and 2013 from the Taiwan National Health Insurance Research Datasets to conduct a population-based matched-cohort study. Controls were 61,550 subjects without Candida infection and propensity score matched with the Candida exposure cohort. The follow-up period was defined as month from the initial diagnosis of Candida infection (or nested index date for controls) to the date of AS, or 31 December 2013. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the occurrence of AS. RESULTS: The incidence rates of AS in the Candida group and comparison groups were 4.58 and 3.88 per 100,000-person months, respectively. The adjusted HR (95% CI) of AS for the Candida group was 1.19 (0.99-1.44) compared to the control group after adjustment for age, gender, and all covariates. (95% CI =1.77-2.27). However, an aHR of 1.77-fold (95% CI: 1.26-2.53) significant increase in the risk of developing AS was observed after 6 years of follow-up, when exposure to Candida was at baseline. The effect of Candida infection was significantly time varying (P value for interaction between follow up period and Candida infection is 0.018). CONCLUSIONS: A risk of AS was found after Candida infection, and year of follow up acts as an effect modifier between the Candida infection and risk of AS. Key message: What is already known on this subject? Links between spondyloarthritis and fungal infections have been found in animal studies before. What does this study add? Our study demonstrated that Candida infection is an independent risk factor for developing ankylosing spondylitis in terms of gender, age, and relevant variables and comorbidities. A risk of ankylosing spondylitis was found after Candida infection, and year of follow up acts as an effect modifier between the Candida infection and risk of AS. Clinicians should be aware of possible Candida infection in managing patients with ankylosing spondylitis. Implications: Clinicians must pay greater attention to patients with newly diagnosed Candida infection. Specifically, they should conduct tests for ankylosing spondylitis. Further research is needed to examine if and how treatment of Candida infection alleviates symptoms of AS.

11.
World Neurosurg ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33059078

RESUMO

OBJECTIVE: A optimized enhanced recovery after surgery (ERAS) is lacking for adolescent idiopathic scoliosis (AIS). The aim of the present study was to evaluate the impact and feasibility of an optimized ERAS pathway in surgically treated AIS patients. METHODS: In total, 79 AIS patients who underwent corrective surgery without 3-column osteotomy were recruited from XiJing Hospital of the Fourth Military Medical University between 2012 and 2018. 44 patients were treated according to a traditional protocol and 35 were managed using an optimized ERAS pathway, which was designed and implemented by a multidisciplinary team. The following data were collected and retrospectively analyzed, demographic characteristics, Cobb angle, curve type (Lenke), surgical duration, fusion level, correction rate, estimated blood loss, postoperative hemoglobin, postoperative pain score, pain relief time, hemovac drainage, drainage removal time, first ambulation time, length of hospital stay (LOS), and postoperative complications. RESULTS: There was no significant difference between the traditional and ERAS groups with respect to demographic characteristics, Cobb angle, curve type (Lenke), fusion level, and correction rate. However, the ERAS group had a shorter surgical duration, less blood loss and hemovac drainage, a higher postoperative hemoglobin level, and earlier pain relief, ambulation and discharge. The rates of postoperative nausea and vomiting were lower in the ERAS group than that in the traditional group. CONCLUSIONS: The ERAS pathway is capable of improving the perioperative status of AIS patients by offering stronger analgesia, faster ambulation, and earlier discharge.

12.
J Immunother Cancer ; 8(2)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33060149

RESUMO

BACKGROUND: Irinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear. METHODS: This multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1. RESULTS: Between October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4-18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS<1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5-12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths. CONCLUSION: The combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study. TRIAL REGISTRATION NUMBER: NCT03704246.

13.
J Am Chem Soc ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063996

RESUMO

Surface states of mesoporous NiO semiconductor films have particular properties differing from the bulk and are able to dramatically influence the interfacial electron transfer and adsorption of chemical species. To achieve a better performance of NiO-based p-type dye-sensitized solar cells (p-DSCs), the function of the surface states has to be understood. In this paper, we applied a modified atomic layer deposition procedure that is able to passivate 72% of the surface states on NiO by depositing a monolayer of Al2O3. This provides us with representative control samples to study the functions of the surface states on NiO films. A main conclusion is that surface states, rather than the bulk, are mainly responsible for the conductivity in mesoporous NiO films. Furthermore, surface states significantly affect dye regeneration (with I-/I3- as redox couple) and hole transport in NiO-based p-DSCs. A new dye regeneration mechanism is proposed in which electrons are transferred from reduced dye molecules to intra-bandgap states, and then to I3- species. The intra-bandgap states here act as catalysts to assist I3- reduction. A more complete mechanism is suggested to understand the particular hole transport behavior in p-DSCs, in which the hole transport time is independent of light intensity. This is ascribed to the percolation hole hopping on the surface states. When the concentration of surface states was significantly reduced, the light-independent charge transport behavior in pristine NiO-based p-DSCs transformed into having an exponential dependence on light intensity, similar to that observed in TiO2-based n-type DSCs. These conclusions on the function of surface states provide new insight into the electronic properties of mesoporous NiO films.

14.
Am J Case Rep ; 21: e924905, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052896

RESUMO

BACKGROUND COVID-19 has been identified as the cause of the large outbreak of pneumonia in patients in Wuhan with shared history of exposure to the Huanan seafood market; however, there is more to learn about this disease. Some experts report that the virus may have reduced toxicity during transmission, but others say that toxicity does not change during transmission. CASE REPORT In this case series, we report clinical and imaging characteristics of 3 patients (A, B, and C) infected with COVID-19. In an exposure-tracking epidemiological investigation, we found that it is possible that Patient A transmitted the infection to her treating physician, Patient B. Patient B then likely transmitted the infection to her family member, Patient C. From the chest CT studies and clinical characteristics, we postulate that the virulence did not decrease during human-to-human transmission. In previous studies, patients with the virus infection had changes in chest CT; however, we found that during the early stages of this disease, some patients (Patient C) may have normal chest CT scans and laboratory studies. Most importantly, we found that IL-6 levels were highest and lymphocyte count was lowest in those with more severe infection. CONCLUSIONS In this case series, we report the exposure relationship of the 3 patients and found that chest CT scans may not have any changes at the beginning of this disease. Lymphopenia and elevated levels of IL-6 can be found after infection.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 118974, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-33010539

RESUMO

We combined the virtues of mesoporous silica and organic functional groups to develop a hybrid fluorescent sensor, PyU-SBA-15, with excellent ability to detect Hg2+ in aqueous medium with high selectivity. In this sensor, the pyrene fluorophore acts as the reporter and the urea unit acts as the receptor during Hg2+ determination. The control material, PyH-SBA-15, which lacks a carbonyl group in the receptor portion, did not display metal-ion selectivity, thereby demonstrating that introducing an additional metal-chelating unit is necessary to improve the metal-ion selectivity of the hybrid sensor. When the concentration of Hg2+ was increased, the fluorescence emission intensities of PyU-SBA-15 at 379, 398, and 476 nm gradually decreased. The emission intensity at 379 nm was linearly proportional to Hg2+ concentrations in the range of 0-1.0 × 10-4 M, and the sensor was determined to have a detection limit of 9.92 × 10-8 M. This work provides an effective strategy for improving or modulating the metal-ion selectivity of fluorescent sensors based on organic-inorganic hybrid mesoporous silica systems.

16.
BMJ Open ; 10(10): e037543, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067279

RESUMO

INTRODUCTION: Many patients with frontal brain damage show serious cognitive function deficits, which hamper their quality of life and result in poor clinical outcomes. Preclinical research has shown that sulforaphane can significantly improve spatial localisation and working memory impairment after brain injury. The primary aim of this double-blind randomised controlled clinical trial is to assess the efficacy of sulforaphane for improving cognitive function in patients with frontal brain damage. METHODS AND ANALYSIS: Ninety eligible patients will be randomly allocated to an active treatment or a placebo group in a 2:1 ratio. Participants will undergo a series of cognitive and neuropsychiatric tests at baseline (week 0) and after 12 weeks to determine the effect of sulforaphane on cognition. Magnetic resonance spectrum of the brain will be studied using the 3T MRIs of the brain to detect brain metabolites markers, including N-acetyl aspartate, glutamate (Glu), glutathione (GSH) and γ-aminobutyric acid (GABA). Blood brain-derived neurotrophic factor, Glu, GSH and GABA levels and gut microbiota will also be assessed over this period. This study will also evaluate long-term outcomes of brain trauma, brain tumours and cerebrovascular disease via exploratory analyses. The primary outcome will be the difference in scores of a battery of cognitive tests after 12 weeks of sulforaphane treatment. The secondary outcomes will be changes in the Functional Activities Questionnaire (FAQ), the Patient Health Questionnaire (PHQ-9), the Self-Rating Anxiety Scale, the changes in T1-weighted MRI and resting-state functional MRI findings, and changes in brain and blood metabolic markers and gut microbiota at weeks 0 and 12. We expect that sulforaphane will yield favourable results in treating memory and learning deficits for patients with frontal brain damage. Cognitive functional treatment may also improve brain trauma, brain tumours and cerebrovascular outcomes. ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethics committee of the Xiangya Hospital of Central South University (No. 2017121019). The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: This trial was registered on Clinicaltrials.gov on 31 January 2020 (NCT04252261). The protocol version is V.1.0 (20 December 2019).

17.
Pediatr Blood Cancer ; : e28767, 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33073479

RESUMO

BACKGROUND: This pilot study explored the feasibility and acceptability of implementing text-based assessments of oral chemotherapy adherence in adolescents and young adults (AYA) with leukemia. METHODS: AYA prescribed maintenance 6-mercaptopurine (6MP) received daily text message surveys and utilized an electronic pill bottle for 28 days. Text surveys assessed 6MP adherence and contextual associates (eg, mood). Feasibility was defined by recruitment/retention rates, survey completion rates, cost, and technical issues. After the 28-day period, AYA completed an acceptability survey. Secondary analyses compared text survey and electronic pill bottle adherence rates, and explored the daily associations between contextual factors and 6MP nonadherence. RESULTS: Eighteen AYA enrolled (M age = 18, range 15-22) and completed study procedures (100% recruitment and retention rates). Adherence survey completion rates were high (M = 88.9%), the technology cost was $204.00, and there were few technical issues. AYA reported high satisfaction with the surveys and perceived them as a helpful medication reminder. While not significantly correlated, survey and electronic pill bottle adherence data converged on the majority of days (>90%). Exploratory analyses showed that AYA were more likely to miss a dose of 6MP on weekends (OR = 2.33, P = .048) and on days when their adherence motivation (OR = 0.28, P = .047) and negative effect (OR = 3.92, P = .02) worsened from their own typical functioning. CONCLUSIONS: For AYA with leukemia, daily text-based surveys are a feasible and acceptable method for delivering medication adherence assessments, and may operate as a short-term intervention. To develop personalized mobile health interventions, findings also highlighted the need to study time-varying predictors of 6MP nonadherence.

18.
Front Immunol ; 11: 2043, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973811

RESUMO

Active co-delivery of tumor antigens (Ag) and α-galactosylceramide (α-GalCer), a potent agonist for invariant Natural Killer T (iNKT) cells, to cross-priming CD8α+ dendritic cells (DCs) was previously shown to promote strong anti-tumor responses in mice. Here, we designed a nanoparticle-based vaccine able to target human CD141+ (BDCA3+) DCs - the equivalent of murine CD8α+ DCs - and deliver both tumor Ag (Melan A) and α-GalCer. This nanovaccine was inoculated into humanized mice that mimic the human immune system (HIS) and possess functional iNKT cells and CD8+ T cells, called HIS-CD8/NKT mice. We found that multiple immunizations of HIS-CD8/NKT mice with the nanovaccine resulted in the activation and/or expansion of human CD141+ DCs and iNKT cells and ultimately elicited a potent Melan-A-specific CD8+ T cell response, as determined by tetramer staining and ELISpot assay. Single-cell proteomics further detailed the highly polyfunctional CD8+ T cells induced by the nanovaccine and revealed their predictive potential for vaccine potency. This finding demonstrates for the first time the unique ability of human iNKT cells to license cross-priming DCs in vivo and adds a new dimension to the current strategy of cancer vaccine development.

19.
BMC Cardiovasc Disord ; 20(1): 423, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962641

RESUMO

BACKGROUND: Familial dilated cardiomyopathy (FDCM) is most commonly inherited as an autosomal dominant trait. The Lamin A/C (LMNA) gene variants have been identified to be associated with DCM, conductive system disorders, type 2 Emery-Dreifuss muscular dystrophy and several other disorders. Here, we reported a novel variant in the LMNA gene that might be related to FDCM. CASE PRESENTATION: A 30-year-old young man was hospitalized for chest tightness, extreme fatigue, palpitation and impaired activity tolerance. He had clinical characteristics including cardiac dilatation, atrial tachyarrhythmia, severe conductive system disorders, and dyskinesia of both upper limbs and the neck. Genetic sequence analysis indicated that the patient carried a novel c.1325 T>C heterozygous LMNA gene variant. Catheter ablation and cardiac resynchronization therapy with pacing function (CRT-P) were performed to treat the arrhythmia. CONCLUSION: The variant c.1325 T>C is a novel variant in the LMNA gene that has not been previously reported. Young patients with DCM, conductive system disorders and skeletal myopathy should be alert to the possibility of LMNA gene variant. Cardiac resynchronization therapy (CRT) may be a reasonable choice for patient carrying a LMNA gene variant with third-degree atrioventricular block even if the left ventricular ejection fraction is preserved in order to prevent the deterioration of cardiac function caused by right ventricular pacing dependency.

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