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1.
Nano Lett ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38901032

RESUMO

Transition metal dichalcogenides (TMDs) are quantum confined systems with interesting optoelectronic properties, governed by Coulomb interactions in the monolayer (1L) limit, where strongly bound excitons provide a sensitive probe for many-body interactions. Here, we use two-dimensional electronic spectroscopy (2DES) to investigate many-body interactions and their dynamics in 1L-WS2 at room temperature and with sub-10 fs time resolution. Our data reveal coherent interactions between the strongly detuned A and B exciton states in 1L-WS2. Pronounced ultrafast oscillations of the transient optical response of the B exciton are the signature of a coherent 50 meV coupling and coherent population oscillations between the two exciton states. Supported by microscopic semiconductor Bloch equation simulations, these coherent dynamics are rationalized in terms of Dexter-like interactions. Our work sheds light on the role of coherent exciton couplings and many-body interactions in the ultrafast temporal evolution of spin and valley states in TMDs.

2.
Int J Mol Sci ; 25(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673867

RESUMO

Sialyltransferase-catalyzed membrane protein and lipid glycosylation plays a vital role as one of the most abundant post-translational modifications and diversification reactions in eukaryotes. However, aberrant sialylation has been associated with cancer malignancy and metastasis. Sialyltransferases thus represent emerging targets for the development of small molecule cancer drugs. Herein, we report the inhibitory effects of a recently discovered lithocholic acid derivative FCW393 on sialyltransferase catalytic activity, integrin sialyation, cancer-associated signal transduction, MDA-MB-231 and B16F10 cell migration and invasion, and in in vivo studies, on tumor growth, metastasis, and angiogenesis. FCW393 showed effective and selective inhibition of the sialyltransferases ST6GAL1 (IC50 = 7.8 µM) and ST3GAL3 (IC50 = 9.45 µM) relative to ST3GAL1 (IC50 > 400 µM) and ST8SIA4 (IC50 > 100 µM). FCW393 reduced integrin sialylation in breast cancer and melanoma cells dose-dependently and downregulated proteins associated with the integrin-regulated FAK/paxillin and GEF/Rho/ROCK pathways, and with the VEGF-regulated Akt/NFκB/HIF-1α pathway. FCW393 inhibited cell migration (IC50 = 2.6 µM) and invasion in in vitro experiments, and in in vivo studies of tumor-bearing mice, FCW393 reduced tumor size, angiogenesis, and metastatic potential. Based on its demonstrated selectivity, cell permeability, relatively low cytotoxicity (IC50 = 55 µM), and high efficacy, FCW393 shows promising potential as a small molecule experimental tool compound and a lead for further development of a novel cancer therapeutic.


Assuntos
Movimento Celular , Sialiltransferases , Sialiltransferases/metabolismo , Sialiltransferases/antagonistas & inibidores , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Metástase Neoplásica , Feminino , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Litocólico/farmacologia
3.
Bioorg Med Chem Lett ; 105: 129760, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38641151

RESUMO

The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MDA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated integrin/FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis.


Assuntos
Ácido Litocólico , Simulação de Acoplamento Molecular , Sialiltransferases , Ácido Litocólico/farmacologia , Ácido Litocólico/química , Ácido Litocólico/síntese química , Ácido Litocólico/análogos & derivados , Humanos , Sialiltransferases/antagonistas & inibidores , Sialiltransferases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Relação Estrutura-Atividade , Sulfatos/química , Sulfatos/farmacologia , Sulfatos/síntese química , Metástase Neoplásica , Ácidos Sulfônicos/farmacologia , Ácidos Sulfônicos/química , Ácidos Sulfônicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Estrutura Molecular , Adesão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Paxilina/metabolismo , Paxilina/antagonistas & inibidores , Quinase 1 de Adesão Focal/antagonistas & inibidores , Quinase 1 de Adesão Focal/metabolismo , Descoberta de Drogas
4.
Indian J Pathol Microbiol ; 67(2): 466-468, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38391381

RESUMO

ABSTRACT: Adult rhabdomyoma is an uncommon and benign striated muscle tumor consisting of striated muscular tissue. This neoplasm usually originates from cardiac muscle, and extracardiac rhabdomyoma is extremely rare. Herein, we report a case of adult rhabdomyoma in the lung, which has only been reported once in the 1970s. A 62-year-old woman presented to our hospital with a solid nodule on the right upper lobe. We performed tumor resection surgery and confirmed the diagnosis of adult rhabdomyoma by postoperative pathological examination. Herein, we report the clinical and pathologic characteristics of pulmonary adult rhabdomyoma (PAR) and review the literature about adult rhabdomyoma.


Assuntos
Neoplasias Pulmonares , Rabdomioma , Humanos , Rabdomioma/patologia , Rabdomioma/diagnóstico , Rabdomioma/cirurgia , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Pulmão/patologia , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Tomografia Computadorizada por Raios X , Imuno-Histoquímica
5.
J Am Med Dir Assoc ; 25(5): 817-825.e5, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38341185

RESUMO

OBJECTIVES: To develop and test the direct and indirect associations between caregiver distress and its many contributing factors and covariates. DESIGN: Analysis using data from a national, cross-sectional survey of Canadian caregivers. SETTING AND PARTICIPANTS: A total of 6502 respondents of the 2012 General Social Survey-Caregiving and Care-receiving who self-identified as a caregiver. METHODS: We used exploratory structural equation modeling to achieve our aims. Based on literature review, we hypothesized a structural model of 5 caregiving factors that contribute to distress: caregiving burden, caregiving network and support, disruptions of family and social life, positive emotional experiences, and caregiving history. Survey items hypothesized to measure each latent factor were modeled using exploratory factor analysis (EFA). After establishing a well-fit EFA model, structural equation modeling was performed to examine the relationships between caregiving factors and caregiver distress while controlling for covariates such as caregiver's and care-recipient's sociodemographic characteristics and kinship. RESULTS: EFA established a well-fit model that represented caregiver distress and its 5 contributing factors as hypothesized. Although all 5 had significant effects on caregiver distress, disruptions of family and social life contributed the most (ß = 0.462), almost 3 times that of caregiving burden (ß = 0.162). Positive emotional experiences also substantially reduced distress (ß = -0.310). CONCLUSIONS AND IMPLICATIONS: Understanding the multifaceted nature of caregiver distress is crucial for developing effective strategies to support caregivers. In addition to reducing caregiving burden, having flexible resources and policies to minimize disruptions to caregivers' families (eg, flexible work policies; family-oriented education, training, and counseling) and enhance the positive aspects of caregiving may more effectively reduce distress.


Assuntos
Cuidadores , Análise de Classes Latentes , Humanos , Masculino , Cuidadores/psicologia , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Canadá , Idoso , Adulto , Inquéritos e Questionários , Estresse Psicológico , Sobrecarga do Cuidador/psicologia , Análise Fatorial , Angústia Psicológica , Apoio Social
6.
Artigo em Inglês | MEDLINE | ID: mdl-38306956

RESUMO

Ion mobility spectrometry (IMS) has a promising application prospect in food surveillance. However, due to the complexity of food matrix and trace levels of pesticide residues, the effective and rapid detection of pesticides by IMS has been a challenge, especially when using electrospray ionization (ESI) as an ion source. In this study, low-temperature partitioning with dispersive solid-phase extraction (LTP-dSPE) was explored and compared with conventional procedures. Both methods were validated for the quantification of eight pesticides in apples, obtaining a limit of detection (LOD) of 0.02-0.12 mg/kg for LTP-dSPE and 0.02-0.09 mg/kg for conventional solid-phase extraction (SPE), lower than those usually stipulated by government legislation in food matrices. For LTP-dSPE, the matrx effect (ME) ranged from -16.3 to -68.6 %, lower than that for the SPE method, ranging from -70.0 to -92.9 %. The results showed satisfactory efficiency and precision, with recovery values ranging from 67.9 to 115.4 % for LTP-dSPE and from 62.0 to 114.8 % for conventional SPE, with relative standard deviations below 13.0 %. Notably, the proposed LTP-dSPE/ESI-IMS has been shown to be more cost-effective, easier to use, more environment-friendly, more accessible, and, most importantly, less matrix effect than the conventional method, thereby being suitably applicable to a wide range of food safety applications.


Assuntos
Malus , Resíduos de Praguicidas , Praguicidas , Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Temperatura , Resíduos de Praguicidas/análise , Espectrometria de Mobilidade Iônica , Extração em Fase Sólida/métodos
7.
CMAJ ; 196(7): E209-E221, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38408785

RESUMO

BACKGROUND: In Canada, only 15% of patients requiring palliative care receive such services in the year before death. We describe health care utilization patterns among home care users in their last 6 months of life to inform care planning for older people with varying mortality risks and evolving care needs as they decline. METHODS: Using population health administrative data from Ontario, we performed a retrospective cohort study involving home care clients aged 50 years and older who received at least 1 interRAI (Resident Assessment Instrument) Home Care assessment between April 2018 and September 2019. We report the proportion of clients who used acute care, long-term care, and palliative home care services within 6 months of their assessment, stratified by their predicted 6-month mortality risk using a prognostic tool called the Risk Evaluation for Support: Predictions for Elder-life in their Communities Tool (RESPECT) and vital status. RESULTS: The cohort included 247 377 adults, 11.9% of whom died within 6 months of an assessment. Among decedents, 50.6% of those with a RESPECT-estimated median survival of fewer than 3 months received at least 1 nonphysician palliative home care visit before death. This proportion declined to 38.7% and 29.5% among decedents with an estimated median survival between 3 and 6 months and between 6 and 12 months, respectively. INTERPRETATION: Many older adults in Ontario do not receive any palliative home care before death. Prognostic tools such as RESPECT may improve recognition of reduced life expectancies and palliative care needs of individuals in their final years of life.


Assuntos
Serviços de Assistência Domiciliar , Assistência Terminal , Humanos , Pessoa de Meia-Idade , Idoso , Cuidados Paliativos/métodos , Estudos Retrospectivos , Atenção à Saúde , Ontário/epidemiologia , Assistência Terminal/métodos
8.
Anal Chem ; 96(6): 2360-2368, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38289229

RESUMO

Ion mobility spectrometry (IMS) is a reliable and sensitive technique for the detection and analysis of compounds at the trace level. Depending on the chemical composition of the sample, compounds may be positively or negatively charged to form different polarity ions and detected in positive or negative polarity of the electric field. In order to detect multiple threats simultaneously with miniaturized devices, using a single detection unit to achieve high resolving power and high sensitivity is important. In this work, a miniaturized drift tube with fast polarity switching capabilities integrated with Fourier deconvolution multiplexing techniques is proposed for the first time as a means to improve the performance of ion mobility spectrometry. The sensitivity and resolving power are improved compared to traditional polarity switching signal averaging data acquisition methods. The displayed device had a high resolving power up to 52 at a drift length of 41 mm and a drift tube voltage of 2 kV. Trinitrotoluene (TNT), methamphetamine (MA), benzene, toluene, methyl tert-butyl ether (MTBE), acetic acid, and methylene chloride were evaluated using the proposed fast polarity switching multiplexing spectrometer and exhibited satisfied performance.

9.
Ann Anat ; 253: 152210, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38244942

RESUMO

BACKGROUND: Osseous condition of the mandible was regarded as a key factor influencing stability of implants in the early stage. Finite element analysis was used to assess the effect of bone mass density and alveolar bone resorption (double factors) on stress in a four-unit implant restoration of a free-end edentulous posterior mandible. METHODS: A 3D finite element model was constructed for a single-sided free-end edentulous mandible (from mandibular first premolar to mandibular second molar) containing threaded dental implants. Mandible sensitivity modes were constructed with different alveolar bone resorption levels for normal conditions as well as mild, moderate and severe periodontitis, respectively. Based on the mass density of cancellous bone for four types of bones as the sensitivity parameter, two implant design modes were constructed: Model A (four-unit fixed bridge supported by three implants, implant positions were 34, 36 and 37) and model B: 34 × 36, 37 (37: a single implant crown) (34 × 36: three-unit fixed bridge supported by two implants, implant positions were 34 and 36). A total of 32 sensitivity-based finite element models, grouped in two groups, were constructed. Stress distribution and maximum von Mises stress on cortical bone and cancellous bone around the implant, as well as the surface of implant were investigated by using ABAQUS when vertical loading and 45° oblique loading were applied, respectively. RESULTS: When vertical loading was applied on the implant, maximum von Mises stress on the cortical bone around the implant was assessed to be 4.726 MPa - 13.15 MPa and 6.254 MPa - 13.79 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 2.641 MPa - 3.773 MPa and 2.864 MPa - 4.605 MPa, respectively; maximum stress on the surface of implant was 14.7 MPa - 21.17 MPa and 21.64 MPa - 30.70 MPa, respectively. When 45° oblique loading was applied on the implant restoration, maximum von Mises stress on the cortical bone around the implant was assessed to be 42.08 MPa - 92.71 MPa and 50.84 MPa - 102.5 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 4.88 MPa - 25.95 MPa and 5.227 MPa - 28.43 MPa, respectively; maximum stress on the surface of implant was 77.91 MPa - 124.8 MPa and 109.2 MPa - 150.7 MPa, respectively. Stress peak on the cortical bone and that on cancellous bone around the implant increased and decreased with the decrease in bone mass density, respectively. Stress peak on alveolar bone increased with alveolar bone resorption when oblique loading was applied. CONCLUSION: 1. Both alveolar bone resorption and bone mass density (double factors) are critical to implant restoration. Bone mass density may exhibit a more pronounced impact than alveolar bone resorption. 2. From the biomechanical perspective, types I and II bones are preferred for implant restoration, while implantation should be considered carefully in the case of type III bones, or those with less bone mass density accompanied by moderate to severe alveolar bone loss. 3. Splinting crowns restoration is biomechanically superior to single crown restoration.


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Humanos , Perda do Osso Alveolar/cirurgia , Análise de Elementos Finitos , Software , Dente Pré-Molar , Mandíbula/cirurgia , Estresse Mecânico , Análise do Estresse Dentário , Prótese Dentária Fixada por Implante
10.
J Palliat Med ; 27(2): 224-230, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37967408

RESUMO

Background: Dying in nonpalliative acute care is generally considered inappropriate and avoidable. Place of death, a commonly reported big-dot indicator of end-of-life care quality, is often used as a proxy for place of care despite no empirical evidence for their correlations. Thus, we examined the correlations between place of death and place of care in the last month of life. We also investigated anecdotal claims that individuals cared in acute care often get discharged to die at home, and vice versa. Methods: We conducted a retrospective cohort study of Ontario decedents (18+) who died between January 1, 2015 and December 31, 2017. We identified individuals who died in nonpalliative acute care, palliative care unit, subacute care, long-term care (LTC), and the community. We calculated the number of days decedents spent in each setting in their last month of life, and used descriptive analyses to investigate their correlations. Results: Decedent's place of death generally correlated with their place of care in the last month of life-individuals who died in a particular setting spent more time in that setting than individuals who died elsewhere. Furthermore, 75.0% of individuals who spent more than two weeks of their last month in acute care died in acute care. Among individuals who died in the community and in LTC, 65.4% and 75.0%, respectively, spent zero days in acute care. Interpretation: We showed that place of death can be a useful high-level performance indicator, by itself and as a proxy for place of care, to gauge end-of-life quality and service provision/implementation.


Assuntos
Assistência Terminal , Humanos , Estudos Retrospectivos , Ontário , Cuidados Paliativos , Morte
11.
Oncol Rep ; 50(6)2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37888767

RESUMO

The heterogeneity of glioblastoma can suppress immune cell function and lead to immune evasion, which presents a challenge in developing effective molecular therapies for tumor cells. However, the study of tumor immune heterogeneity holds great potential for clinical immunotherapy. Liquid biopsy is a useful tool for accurately monitoring dynamic changes in tumor immune heterogeneity and the tumor microenvironment. This paper explores the heterogeneity of glioblastoma and the immune microenvironment, providing a therapeutic basis for individualized treatment. Using liquid biopsy technology as a new diagnostic method, innovative treatment strategies may be implemented for patients with glioblastoma to improve their outcomes.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Imunoterapia/métodos , Biópsia Líquida , Microambiente Tumoral
12.
Front Immunol ; 14: 1260705, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781382

RESUMO

The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the anti-tumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy.


Assuntos
Interferon Tipo I , Neoplasias , Humanos , Transdução de Sinais , Imunidade Inata/fisiologia , Imunidade Adaptativa , DNA , RNA
13.
Brain Res Bull ; 202: 110761, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37714275

RESUMO

Aging-related cognitive impairment (ARCI) is rapidly becoming a healthcare priority. However, there is currently no excellent cure for it. Cognitive-exercise dual-task intervention (CEDI) is a promising method to improve ARCI, while the underlying mechanisms remain unclear. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the onset, development, and rehabilitation of ARCI. This study aimed to investigate the effects of CEDI and the role of regulation of the lncRNA NEAT1/miR-124-3p on the caveolin-1-PI3K/Akt/GSK3ß pathway in CEDI improving cognitive function. Forty 18-month-old natural aging rats were randomly assigned to four groups: exercise training group, cognitive training group, CEDI group, and aging control group, and underwent 12 weeks of intervention. A novel object recognition test was performed to determine the cognitive function, and the hippocampus was separated three days after the behavioral tests for further molecular detection. In an in vitro study, the mouse hippocampal neuronal cell line HT22 was cultured. MiR-124-3p and lncRNA NEAT1 were over-expressed or down-expressed, respectively. The expressions of related proteins, lncRNA, and miRNA were examined by WB and/or qRT-PCR. The results showed that compared with the aging control group, the CEDI group had a higher discrimination index, and significantly decreased the expressions of lncRNA NEAT1, and the protein expressions of caveolin-1 and p-GSK3ß, while significantly increased the expressions of miR-124-3p, and the protein expressions of p-PI3K and p-Akt. Inhibition of the lncRNA NEAT1 could significantly increase the protein expressions of p-PI3K and p-Akt in HT22 cells. Upregulation of miR-124-3p decreased the protein expressions of caveolin-1 and p-GSK3ß, and increased the protein expressions of p-PI3K and p-Akt significantly. Inhibition of miR-124-3p had the opposite effects. Our study demonstrated that CEDI improved cognitive function in aging rats better than a single intervention. The mechanisms of cognitive improvement could be related to the regulation of the lncRNA NEAT1/miR-124-3p on the caveolin-1-PI3K/Akt/GSK3ß pathway.


Assuntos
Disfunção Cognitiva , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Ratos , Envelhecimento , Caveolina 1 , Cognição , Disfunção Cognitiva/terapia , Glicogênio Sintase Quinase 3 beta , MicroRNAs/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante/genética
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 301: 122956, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37302197

RESUMO

The neutral rhenium(I)-biimidazole complex [Re(CO)3(biimH)(1,4-NVP)] (1) was designed and synthesized by a one-pot reaction of Re2(CO)10, 2,2'-biimidazole (biimH2) and 4-(1-naphthylvinyl)pyridine (1,4-NVP). The structure of 1 was characterized by various spectroscopic techniques including IR, 1H NMR, FAB-MS, and elemental analysis and further confirmed by a single-crystal X-ray diffraction analysis. The mononuclear complex 1, a relatively simple structure with an octahedral geometry, is comprised of facial-arranged carbonyl groups, one chelated biimH monoanion, and one 1,4-NVP. Complex 1 shows the lowest energy absorption band at around 357 nm and an emission band at 408 nm in THF. The luminescent characteristics of 1 combined with the hydrogen bonding ability of the partially coordinated monoionic biimidazole ligand permits the complex to selectively recognize fluoride ions (F-) in the presence of other halides through a dramatic luminescence enhancement. The recognition mechanism of 1 can be convincingly explained in terms of H-bond formation and proton abstraction upon the addition of F- ions by 1H and 19F NMR titration experiments. The electronic properties of 1 were further supported by time dependent density functional theory (TDDFT) computational studies.


Assuntos
Rênio , Rênio/química , Fluoretos , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Teoria da Densidade Funcional , Prótons
15.
BMJ Open ; 13(5): e069251, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37130662

RESUMO

INTRODUCTION: Hyperglycaemia during pregnancy has been considered as one of the risk factors for cardiovascular diseases (CVDs) among women. Although the evidence regarding the association between gestational diabetes mellitus (GDM) and subsequent CVD has been synthesised, there are no systematic reviews covering the evidence of the association among the non-GDM population. This systematic review and meta-analysis, therefore, aim to fill the gap by summarising existing evidence on the association between maternal glucose levels and the risk of future CVD in pregnant women with or without a diagnosis of GDM. METHODS AND ANALYSIS: This systematic review protocol was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. Comprehensive literature searches were performed in the following electronic databases: MEDLINE, EMBASE and CINAHL to identify relevant papers from inception to 31 December 2022. All observational studies (case-control studies, cohort studies and cross-sectional studies) will be included. Two reviewers will perform the abstract and full-text screening based on the eligibility criteria through Covidence. The Newcastle-Ottawa Scale will be used to assess the methodological quality of included studies. Statistical heterogeneity will be assessed by using the I2 test and Cochrane's Q test. If the included studies are found to be homogeneous, pooled estimates will be calculated and meta-analysis will be performed using Review Manager 5 (RevMan) software. Random effects will be used to determine weights for meta-analysis, if needed. Pre-specified subgroup analysis and sensitivity analysis will be performed, if needed. The study results will be presented in the sequence of main outcomes, secondary outcomes and important subgroup analysis for each type of glucose level separately. ETHICS AND DISSEMINATION: Given no original data will be collected, ethics approval is not applicable for this review. The results of this review will be disseminated by publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42022363037.


Assuntos
Doenças Cardiovasculares , Diabetes Gestacional , Hiperglicemia , Gravidez , Feminino , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Diabetes Gestacional/epidemiologia , Glucose , Metanálise como Assunto , Revisões Sistemáticas como Assunto
16.
Front Oncol ; 13: 1094974, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035177

RESUMO

Background: Although minimally invasive surgery is the standard treatment for thymomas, minimally invasive thymectomy is difficult for patients with type B3 thymomas, especially for giant or aggressive lesions. These tumors are frequently treated with radical radiation therapy or surgery plus adjuvant radiotherapy. Few studies, however, have tested the efficacy of neoadjuvant radiotherapy prior to thoracoscopic surgery. Methods: Patients with type B3 thymomas >5 cm or with infiltrates into vital organs on CT-guided puncture biopsy who underwent neoadjuvant radiotherapy followed by single-incision minimally invasive thymectomy from March 2016 to July 2020 were retrospectively evaluated. Reduction ratios, TNM stage changes according to WHO stage criteria, resectability, long-term survival, and the response in terms of RECIST v1.1 criteria achieved by preoperative RT were analyzed. Results: The 11 patients who underwent neoadjuvant radiotherapy plus minimally invasive thymectomy included five men and six women, of mean age 49.5 years. Four patients had myasthenia gravis. Neoadjuvant radiotherapy consisted of 50 Gy in 25 fractions, with all patients showing varying degrees of lesion reduction after radiotherapy. Surgery was performed about 1 month after neoadjuvant radiotherapy, with none of these patients having severe radiation pneumonitis. All patients underwent radical resection of the tumor and adjacent tissue, with none experiencing tumor seeding or rupture during surgery. The median postoperative hospital stay was 3 days (range: 2-6 days) and the frequency of additional regular analgesics (including those for wound pain and neuralgia) was 2.5 times per person. On follow-up, one patient experienced pleural metastasis and one experienced pulmonary metastasis, with the other nine patients showing no evidence of tumor recurrence. Conclusion: Neoadjuvant radiotherapy followed by minimally invasive surgery was a safe and efficacious procedure for the treatment of type B3 thymomas, with less postoperative pain and faster recovery. This strategy, of tumor shrinkage prior to surgery, may make possible the easier removal of type B3 thymomas by single-incision thoracoscopy.

17.
Anal Chim Acta ; 1256: 341123, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37037627

RESUMO

Sensitivity and selectivity are critical parameters to evaluate the performance of sensors. For trace detection, it remains a challenge to design a new sensor that achieves high sensitivity and selectivity simultaneously. Here, we present a target-activated dual Mg2+-dependent DNAzyme (MNAzyme) that served as a simple sensing model to explore the multivalency in improving the analytical sensitivity and selectivity for target detection. Mercury ion (Hg2+), a notorious toxic metal ion, was selected as a model target. In the presence of Hg2+, the thymine-rich regions of the hairpin probe and primer could hybridize to form a stable duplex via the thymine-Hg2+-thymine structure. Then, an intact enzyme sequence was exposed and two separate enzyme fragments were close to each other, generating a dual MNAzyme. Benefiting from the localized high-concentration of the enzyme strand, the dual MNAzyme showed a remarkable improvement in binding stability. The catalytic rate constant of the dual MNAzyme was theoretically 1.60 times higher than that of the monomeric counterpart, and the sensitivity and selectivity had 4.50 and 1.44-fold enhancement, respectively. When the dual MNAzyme was used for sensor applications, the limit of detection was determined to be 0.04 and 0.2 nM via UV-vis spectrophotometer and naked eye, respectively. Meanwhile, the method offered desirable selectivity toward Hg2+ against other metal ions. With the advantages of simple operation, high sensitivity, and desirable selectivity, the developed multivalent sensing platform could be easily expanded in the future for the on-site detection of other low-abundance analytes.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Mercúrio , Timina , DNA Catalítico/química , Espectrofotometria , Mercúrio/química , Catálise , Íons , Técnicas Biossensoriais/métodos , Limite de Detecção
18.
Gerontology ; 69(7): 839-851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37068467

RESUMO

INTRODUCTION: Family/friend caregivers play an essential role in promoting the physical and mental health of older adults in need of care - especially during the COVID-19 pandemic and especially in assisted living (AL) homes, where resident care needs are similarly complex as in long-term care homes but fewer staffing resources and services are available. However, little research is available on caregiver involvement and concerns with care of AL residents prior to and during waves 1 and 2 of the COVID-19 pandemic. This study addressed this important knowledge gap. METHODS: This prospective cohort study used baseline and follow-up online surveys with primary caregivers to AL residents in Western Canada who were 65 years or older and had lived in the AL home for at least 3 months before Mar 1, 2020. Surveys assessed the following outcomes in the 3 months prior to and during waves 1 and 2 of the pandemic: sociodemographics, 5 ways of visiting or communicating with residents, involvement in 16 care tasks, concerns with 9 resident physical/mental health conditions, perceived lack of resident access to 7 care services, and whether caregivers felt well informed and involved with resident care. RESULTS: Based on 386 caregiver responses, in-person visits dropped significantly in wave 1 of the pandemic and so did caregiver involvement in nearly all care tasks. While these rates increased in wave 2, most did not return to pre-pandemic levels. Correspondingly, caregiver concerns (already high before the pandemic) substantially increased in wave 1 and stayed high in wave 2. These were particularly elevated among caregivers who did not feel well informed/involved with resident care. CONCLUSIONS: Restricted in-person visiting disrupted resident care and was associated with worse perceptions of resident health and well-being. Continued caregiver involvement in resident care and communication with caregivers even during lockdowns is key to mitigating these issues.


Assuntos
COVID-19 , Cuidadores , Humanos , Idoso , Cuidadores/psicologia , COVID-19/epidemiologia , Pandemias , Estudos Prospectivos , Controle de Doenças Transmissíveis
19.
BMC Public Health ; 23(1): 225, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732719

RESUMO

BACKGROUND: Empowering adolescent girls is an important component of combating malnutrition in this age group. Because empowerment is multidimensional and context specific, it can be difficult for policymakers and practitioners to target the dimensions of empowerment associated with adolescent girls' nutrition in a particular setting. This study sought to identify the empowerment dimensions significantly associated with married adolescent girls' nutritional status in East Africa; a region where malnutrition and gender inequality stubbornly persist. METHODS: We used cross-sectional Demographic and Health Survey (DHS) data from Ethiopia (2016), Kenya (2014), Tanzania (2015-16) and Uganda (2016) to construct and test theoretically informed structural equation models of the relationship between six dimensions of empowerment and BMI-for-age and haemoglobin levels for married adolescent girls aged 15-19 years. RESULTS: Our models were found to be a good fit for the data. Married adolescent girls' access to information, measured by their education level and mass media use, was directly and positively associated with their BMI-for-age (p < 0.05). Asset ownership, measured by owning a house or land alone or jointly, was directly and positively associated with haemoglobin (p < 0.05) and reduced odds of being moderately to severely anemic. Rejecting justifications for intimate partner violence, a measure of respondents' intrinsic agency, was directly and positively associated with the odds of being overweight or obese. Adolescent girls' level of empowerment across all dimensions had a direct relationship with their country of residence and household wealth. CONCLUSIONS: Our findings suggest that investment in girls' access to information through education and mass/social media and their economic empowerment may be important contributors to their overall empowerment and nutritional status. However, caution is needed as greater autonomy may contribute to increased consumption of unhealthy foods that can contribute to overweight and obesity. Strategies to empower married adolescent girls should be tailored to their specific circumstances. There is an urgent need for better data on adolescent empowerment and health, including increased research into age-, sex- and gender-appropriate empowerment measures and longitudinal data to assess causality. The use of statistical models should be complemented by robust qualitative research to further results interpretation.


Assuntos
Desnutrição , Estado Nutricional , Feminino , Humanos , Adolescente , Análise de Classes Latentes , Estudos Transversais , Sobrepeso , Tanzânia/epidemiologia , Desnutrição/epidemiologia
20.
Anticancer Drugs ; 34(5): 699-706, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730477

RESUMO

Although neoadjuvant target therapy has been used to treat patients with non-small-cell lung cancer (NSCLC), most of these patients have mutations in the epidermal growth factor receptor (EGFR) gene. Few patients to date have received neoadjuvant target therapy for NSCLC containing variants in genes encoding anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). Herein, we present a 51-year-old man with a lung mass in the left lower lobe with enlarged mediastinal lymph nodes. He was diagnosed with NSCLC after needle lung biopsy, with next-generation sequencing showing an echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase (EML4-ALK) fusion variant. The patient received neoadjuvant ensartinib, a second-generation ALK-TKI, for 5 months, followed by successful lobectomy through uniportal video-assisted thoracic surgery and adjuvant ensartinib. To our knowledge, few patients with ALK-positive NSCLC had received neoadjuvant treatment with ensartinib. Findings in this patient may widen indications for neoadjuvant target therapy in the treatment of resectable stage II-IIIA ALK-positive NSCLC.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Inibidores de Proteínas Quinases/farmacologia , Proteínas de Fusão Oncogênica/metabolismo
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