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1.
ANZ J Surg ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847122

RESUMO

BACKGROUND: Haemorrhoidectomy is the gold standard for definitive treatment of high-grade symptomatic haemorrhoids but is often associated with substantial pain. This systematic review aims to explore the potential of flavonoids in alleviating the postoperative symptom burden following excisional haemorrhoidectomy. METHODS: A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD42023472711). Randomized controlled trials (RCTs) published PubMed, MEDLINE, Embase, and Scopus from inception to 1st December 2023 were retrieved. The primary outcome investigated was post-operative pain. Meta-analysis was performed using Review Manager version 5.4.1. RESULTS: Ten articles with 775 patients were included. The meta-analysis identified statistically significant decreases in post-operative pain in favour of the flavonoid groups (Standardized Mean Difference -0.66 [95% confidence intervals (CI) -0.82, -0.52]; P < 0.00001), and bleeding (Odds Ratio 0.13 [95% CI 0.09, 0.19]; P < 0.00001). CONCLUSION: Flavonoids show promise as a means of reducing pain associated with excisional haemorrhoidectomy. Further research is required to investigate topical routes of administration and standardize regimes.

2.
Cancer Nurs ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527112

RESUMO

BACKGROUND: Interactive features of computerized cognitive training (CCT) may enhance adherence to training, providing a relatively low-cost intervention. A robust systematic review on the effectiveness of CCT for improving working memory (WM) among pediatric survivors with cancer is lacking. OBJECTIVE: To summarize the available evidence and determine the effectiveness of CCT for WM among pediatric survivors with cancer. INTERVENTIONS/METHODS: Five databases were searched. The Effective Public Health Practice Project was used to assess the study quality. ReviewerManager was used. The primary outcome was WM performance. Secondary outcomes included processing speed, attention, intervention adherence, and number of adverse events. RESULTS: Six studies were included. Regarding overall quality, 1 study was weak, and 5 studies were moderate. Five studies reported a significant improvement of WM postintervention (P < .05). The meta-analysis of Cogmed interventions on symbolic WM revealed a significant difference between groups (vs placebo), with an overall pooled effect size of 0.71 (95% confidence interval, 0.02-1.41; P = .04). Two and 4 studies investigated the effects of CCT on processing speed and attention, respectively, with conflicting results. Four studies reported adherence of 80% or greater. Two studies reported no adverse events. CONCLUSIONS: Computerized cognitive training using Cogmed has a significant positive effect on WM. The effects of CCT on processing speed and attention remain inconclusive. IMPLICATIONS FOR PRACTICE: More rigorous trials should be conducted to elucidate the cognitive effects of CCT, particularly processing speed and attention, in the pediatric population with cancer. Further studies should consider combining CCT with other existing interventions to strengthen their effectiveness.

3.
Open Biol ; 13(3): 220326, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36883283

RESUMO

Polo-like kinase I (Plk1) is a highly conserved seronine/threonine kinase essential in meiosis and mitosis for spindle formation and cytokinesis. Here, through temporal application of Plk1 inhibitors, we identify a new role for Plk1 in the establishment of cortical polarity essential for highly asymmetric cell divisions of oocyte meiosis. Application of Plk1 inhibitors in late metaphase I abolishes pPlk1 from spindle poles and prevents the induction of actin polymerization at the cortex through inhibition of local recruitment of Cdc42 and Neuronal Wiskott-Aldrich Syndrome protein (N-WASP). By contrast, an already established polar actin cortex is insensitive to Plk1 inhibitors, but if the polar cortex is first depolymerized, Plk1 inhibitors completely prevent its restoration. Thus, Plk1 is essential for establishment but not maintenance of cortical actin polarity. These findings indicate that Plk1 regulates recruitment of Cdc42 and N-Wasp to coordinate cortical polarity and asymmetric cell division.


Assuntos
Actinas , Meiose , Oócitos , Actinas/genética , Actinas/fisiologia , Meiose/genética , Meiose/fisiologia , Oócitos/fisiologia , Polimerização , Proteínas Serina-Treonina Quinases , Quinase 1 Polo-Like
4.
Can Commun Dis Rep ; 49(7-8): 229-309, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38455876

RESUMO

Background: Enteric infections and their chronic sequelae are a major cause of disability and death. Despite the increasing use of administrative health data in measuring the burden of chronic diseases in the population, there is a lack of validated International Classification of Disease (ICD) code-based case definitions, particularly in the Canadian context. Our objective was to validate ICD code definitions for sequelae of enteric infections in Canada: acute kidney injury (AKI); hemolytic uremic syndrome (HUS); thrombotic thrombocytopenic purpura (TTP); Guillain-Barré syndrome/Miller-Fisher syndrome (GBS/MFS); chronic inflammatory demyelinating polyneuropathy (CIDP); ankylosing spondylitis (AS); reactive arthritis; anterior uveitis; Crohn's disease, ulcerative colitis, celiac disease, erythema nodosum (EN); neonatal listeriosis (NL); and Graves' disease (GD). Methods: We used a multi-step approach by conducting a literature review to identify existing validated definitions, a clinician assessment of the validated definitions, a chart review to verify proposed definitions and a final clinician review. We measured the sensitivity and positive predictive value (PPV) of proposed definitions. Results: Forty studies met inclusion criteria. We identified validated definitions for 12 sequelae; clinicians developed three (EN, NL, GD). We reviewed 181 charts for 6 sequelae (AKI, HUS, TTP, GBS/MFS, CIDP, AS). Sensitivity (42.8%-100%) and PPV (63.6%-100%) of ICD code definitions varied. Six definitions were modified by clinicians following the chart review (AKI, TTP, GBS/MFS, CIDP, AS, reactive arthritis) to reflect coding practices, increase specificity or sensitivity, and address logistical constraints. Conclusion: The multi-step design to derive ICD code definitions provided flexibility to identify existing definitions, to improve their sensitivity and PPV and adapt them to the Canadian context.

5.
Sci Adv ; 8(24): eabl8070, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35704569

RESUMO

Eggs contain about 200,000 mitochondria that generate adenosine triphosphate and metabolites essential for oocyte development. Mitochondria also integrate metabolism and transcription via metabolites that regulate epigenetic modifiers, but there is no direct evidence linking oocyte mitochondrial function to the maternal epigenome and subsequent embryo development. Here, we have disrupted oocyte mitochondrial function via deletion of the mitochondrial fission factor Drp1. Fission-deficient oocytes exhibit a high frequency of failure in peri- and postimplantation development. This is associated with altered mitochondrial function, changes in the oocyte transcriptome and proteome, altered subcortical maternal complex, and a decrease in oocyte DNA methylation and H3K27me3. Transplanting pronuclei of fertilized Drp1 knockout oocytes to normal ooplasm fails to rescue embryonic lethality. We conclude that mitochondrial function plays a role in establishing the maternal epigenome, with serious consequences for embryo development.


Assuntos
Desenvolvimento Embrionário , Oócitos , Citoplasma/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Desenvolvimento Embrionário/genética , Feminino , Humanos , Mitocôndrias/metabolismo , Oócitos/metabolismo , Gravidez
6.
Biol Reprod ; 106(2): 366-377, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35094043

RESUMO

The development of oocytes and early embryos is dependent on mitochondrial ATP production. This reliance on mitochondrial activity, together with the exclusively maternal inheritance of mitochondria in development, places mitochondria as central regulators of both fertility and transgenerational inheritance mechanisms. Mitochondrial mass and mtDNA content massively increase during oocyte growth. They are highly dynamic organelles and oocyte maturation is accompanied by mitochondrial trafficking around subcellular compartments. Due to their key roles in generation of ATP and reactive oxygen species (ROS), oocyte mitochondrial defects have largely been linked with energy deficiency and oxidative stress. Pharmacological treatments and mitochondrial supplementation have been proposed to improve oocyte quality and fertility by enhancing ATP generation and reducing ROS levels. More recently, the role of mitochondria-derived metabolites in controlling epigenetic modifiers has provided a mechanistic basis for mitochondria-nuclear crosstalk, allowing adaptation of gene expression to specific metabolic states. Here, we discuss the multi-faceted mechanisms by which mitochondrial function influence oocyte quality, as well as longer-term developmental events within and across generations.


Assuntos
Fertilidade , Mitocôndrias , Oócitos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Oócitos/metabolismo , Oogênese/genética , Espécies Reativas de Oxigênio/metabolismo
7.
Int J Environ Health Res ; 32(3): 547-564, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32579032

RESUMO

Our scoping review aimed to identify and describe the application of digital technology in hand hygiene research among children in educational settings. We searched for articles in PubMed, IEEE Xplore, and Web of Science. Original hand hygiene research with a form of digital technology used among children ≤12 years in educational settings was eligible for inclusion. Twelve studies met the eligibility criteria and the data were extracted by two teams of independent co-authors for narrative synthesis. Ten studies used digital technology as an intervention tool and two for monitoring purposes. Three main digital technologies were identified including computer games (n = 2), videos (n = 8), and video cameras (n = 2). Digital technologies found in our scoping review were reported to be effective in hand hygiene studies over short temporal periods especially when used in combination with other measures. Future research may demonstrate the effectiveness of digital technology in helping children develop sustainable handwashing behaviors.


Assuntos
Tecnologia Digital , Higiene das Mãos , Criança , Desinfecção das Mãos , Humanos
8.
J Youth Adolesc ; 51(5): 927-939, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34704167

RESUMO

Child maltreatment represents a prevalent public health issue that has been shown to predict both adolescent and young adult depressive symptoms and heavy episodic drinking; however, little is known regarding how associations between specific types of maltreatment (e.g., physical abuse, sexual abuse, care neglect, supervisory neglect) and depressive symptoms and heavy episodic drinking change across adolescence and into young adulthood. Similarly, there is lack of research that has examined how an accumulation of child maltreatment types relates to depressive symptoms and heavy episodic drinking across ages. Time-varying effect models-a statistical approach that allows researchers to pinpoint specific ages where the association between two variables is strongest-were used in the current study to address these gaps. Nationally representative data came from the first four waves of the National Longitudinal Study of Adolescent to Adult Health (Add Health; N = 16,053; 49.4% female; 51.0% European American/White, 21.0% African American, 10.2% Biracial, 9.1% Hispanic; MAGE W1 = 17.00). Results suggested that certain types of maltreatment are more predictive of negative outcomes than others and that different types of maltreatment confer greater risk in different developmental periods. In addition, while victims of between one and three types of maltreatment had comparable prevalence of depressive symptoms and heavy episodic drinking across adolescence and young adulthood, victims of four types of maltreatment had a much higher prevalence of these outcomes indicating the extreme risk that accompanies an accumulation of maltreatment.


Assuntos
Maus-Tratos Infantis , Depressão , Adolescente , Adulto , Negro ou Afro-Americano , Criança , Depressão/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , População Branca , Adulto Jovem
9.
ChemSusChem ; 15(3): e202102538, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-34907650

RESUMO

Dimethyl sulfide, a major byproduct of the Kraft pulping process, was used as an inexpensive and sustainable catalyst/co-reagent (methyl donor) for various methylations with dimethyl carbonate (as both reagent and solvent), which afforded excellent yields of O-methylated phenols and benzoic acids, and mono-C-methylated arylacetonitriles. Furthermore, these products could be isolated using a remarkably straightforward workup and purification procedure, realized by dimethyl sulfide's neutral and distillable nature and the absence of residual salts. The likely mechanisms of these methylations were elucidated using experimental and theoretical methods, which revealed that the key step involves the generation of a highly reactive trimethylsulfonium methylcarbonate intermediate. The phenol methylation process represents a rare example of a Williamson-type reaction that occurs without the addition of a Brønsted base.


Assuntos
Formiatos , Sais , Metilação , Sulfetos
10.
Mol Hum Reprod ; 27(11)2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34590701

RESUMO

PIWI-interacting small RNAs (piRNAs) maintain genome stability in animal germ cells, with a predominant role in silencing transposable elements. Mutations in the piRNA pathway in the mouse uniformly lead to failed spermatogenesis and male sterility. By contrast, mutant females are fertile. In keeping with this paradigm, we previously reported male sterility and female fertility associated with loss of the enzyme HENMT1, which is responsible for stabilising piRNAs through the catalysation of 3'-terminal 2'-O-methylation. However, the Henmt1 mutant females were poor breeders, suggesting they could be subfertile. Therefore, we investigated oogenesis and female fertility in these mice in greater detail. Here, we show that mutant females indeed have a 3- to 4-fold reduction in follicle number and reduced litter sizes. In addition, meiosis-II mutant oocytes display various spindle abnormalities and have a dramatically altered transcriptome which includes a down-regulation of transcripts required for microtubule function. This down-regulation could explain the spindle defects observed with consequent reductions in litter size. We suggest these various effects on oogenesis could be exacerbated by asynapsis, an apparently universal feature of piRNA mutants of both sexes. Our findings reveal that loss of the piRNA pathway in females has significant functional consequences.


Assuntos
Fertilidade , Infertilidade Feminina/enzimologia , Meiose , Metiltransferases/metabolismo , Oócitos/enzimologia , Oogênese , RNA Interferente Pequeno/metabolismo , Animais , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Infertilidade Feminina/genética , Infertilidade Feminina/fisiopatologia , Metiltransferases/genética , Camundongos , RNA Interferente Pequeno/genética , Transcriptoma
11.
Nat Commun ; 12(1): 5315, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493720

RESUMO

Human PAK4 is an ubiquitously expressed p21-activated kinase which acts downstream of Cdc42. Since PAK4 is enriched in cell-cell junctions, we probed the local protein environment around the kinase with a view to understanding its location and substrates. We report that U2OS cells expressing PAK4-BirA-GFP identify a subset of 27 PAK4-proximal proteins that are primarily cell-cell junction components. Afadin/AF6 showed the highest relative biotin labelling and links to the nectin family of homophilic junctional proteins. Reciprocally >50% of the PAK4-proximal proteins were identified by Afadin BioID. Co-precipitation experiments failed to identify junctional proteins, emphasizing the advantage of the BioID method. Mechanistically PAK4 depended on Afadin for its junctional localization, which is similar to the situation in Drosophila. A highly ranked PAK4-proximal protein LZTS2 was immuno-localized with Afadin at cell-cell junctions. Though PAK4 and Cdc42 are junctional, BioID analysis did not yield conventional cadherins, indicating their spatial segregation. To identify cellular PAK4 substrates we then assessed rapid changes (12') in phospho-proteome after treatment with two PAK inhibitors. Among the PAK4-proximal junctional proteins seventeen PAK4 sites were identified. We anticipate mammalian group II PAKs are selective for the Afadin/nectin sub-compartment, with a demonstrably distinct localization from tight and cadherin junctions.


Assuntos
Junções Intercelulares/metabolismo , Proteínas dos Microfilamentos/genética , Nectinas/genética , Proteômica/métodos , Proteína cdc42 de Ligação ao GTP/genética , Quinases Ativadas por p21/genética , Biotina/química , Carbono-Nitrogênio Ligases/genética , Carbono-Nitrogênio Ligases/metabolismo , Linhagem Celular Tumoral , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Junções Intercelulares/genética , Junções Intercelulares/ultraestrutura , Marcação por Isótopo , Espectrometria de Massas , Proteínas dos Microfilamentos/metabolismo , Nectinas/metabolismo , Osteoblastos/metabolismo , Osteoblastos/ultraestrutura , Ligação Proteica , Mapeamento de Interação de Proteínas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais , Proteína cdc42 de Ligação ao GTP/metabolismo , Quinases Ativadas por p21/metabolismo
12.
Disaster Med Public Health Prep ; : 1-10, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33762027

RESUMO

OBJECTIVE: This study aimed to investigate coronavirus disease (COVID-19) epidemiology in Alberta, British Columbia, and Ontario, Canada. METHODS: Using data through December 1, 2020, we estimated time-varying reproduction number, Rt, using EpiEstim package in R, and calculated incidence rate ratios (IRR) across the 3 provinces. RESULTS: In Ontario, 76% (92 745/121 745) of cases were in Toronto, Peel, York, Ottawa, and Durham; in Alberta, 82% (49 878/61 169) in Calgary and Edmonton; in British Columbia, 90% (31 142/34 699) in Fraser and Vancouver Coastal. Across 3 provinces, Rt dropped to ≤ 1 after April. In Ontario, Rt would remain < 1 in April if congregate-setting-associated cases were excluded. Over summer, Rt maintained < 1 in Ontario, ~1 in British Columbia, and ~1 in Alberta, except early July when Rt was > 1. In all 3 provinces, Rt was > 1, reflecting surges in case count from September through November. Compared with British Columbia (684.2 cases per 100 000), Alberta (IRR = 2.0; 1399.3 cases per 100 000) and Ontario (IRR = 1.2; 835.8 cases per 100 000) had a higher cumulative case count per 100 000 population. CONCLUSIONS: Alberta and Ontario had a higher incidence rate than British Columbia, but Rt trajectories were similar across all 3 provinces.

13.
Hum Reprod ; 36(3): 771-784, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33367783

RESUMO

STUDY QUESTION: Do mitochondria-targeted therapies reverse ageing- and oxidative stress-induced spindle defects in oocytes from mice and humans? SUMMARY ANSWER: Exposure to MitoQ or BGP-15 during IVM protected against spindle and chromosomal defects in mouse oocytes exposed to oxidative stress or derived from reproductively aged mice whilst MitoQ promoted nuclear maturation and protected against chromosomal misalignments in human oocytes. WHAT IS KNOWN ALREADY: Spindle and chromosomal abnormalities in oocytes are more prevalent with maternal aging, increasing the risk of aneuploidy, miscarriage and genetic disorders such as Down's syndrome. The origin of compromised oocyte function may be founded in mitochondrial dysfunction and increased reactive oxygen species (ROS). STUDY DESIGN, SIZE, DURATION: Oocytes from young and old mice were treated with MitoQ and/or BGP-15 during IVM. To directly induce mitochondrial dysfunction, oocytes were treated with H2O2, and then treated the MitoQ and/or BGP-15. Immature human oocytes were cultured with or without MitoQ. Each experiment was repeated at least three times, and data were analyzed by unpaired-sample t-test or chi-square test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immature germinal vesicle (GV) stage oocytes from 1-, 12- and 18-month-old mice were obtained from preovulatory ovarian follicles. Oocytes were treated with MitoQ and/or BGP-15 during IVM. GV-stage human oocytes were cultured with or without MitoQ. Mitochondrial membrane potential and mitochondrial ROS were measured by live-cell imaging. Meiotic spindle and chromosome alignments were visualized by immunofluorescent labeling of fixed oocytes and the 3-dimensional images were analyzed by Imaris. MAIN RESULTS AND THE ROLE OF CHANCE: MitoQ or BGP-15 during IVM protects against spindle and chromosomal defects in oocytes exposed to oxidative stress and in oocytes from aged mice (P < 0.001). In human oocytes, the presence of MitoQ during IVM promoted nuclear maturation and had a similar positive effect in protecting against chromosomal misalignments (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Our study identifies two excellent candidates that may help to improve fertility in older women. However, these potential therapies must be tested for efficacy in clinical IVM systems, and undergo thorough examination of resultant offspring in preclinical models before utilization. WIDER IMPLICATIONS OF THE FINDINGS: Our results using in-vitro systems for oocyte maturation in both mouse and human provide proof of principle that mitochondrially targeted molecules such as MitoQ and BGP-15 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities. STUDY FUNDING/COMPETING INTEREST(S): The project was financially supported by the National Health and Medical Research Council and Australian Research Council, Australia. U.A.-Z. was supported by the Iraqi Higher Education and Scientific Research Ministry PhD scholarship and O.C. was supported by TUBITAK-1059B191601275. M.P.M. consults for MitoQ Inc. and holds patents in mitochondria-targeted therapies. R.L.R. is an inventor on patents relating to the use of BGP-15 to improve gamete quality. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Peróxido de Hidrogênio , Oócitos , Idoso , Animais , Austrália , Humanos , Peróxido de Hidrogênio/metabolismo , Técnicas de Maturação in Vitro de Oócitos , Camundongos , Mitocôndrias , Oócitos/metabolismo , Oximas , Piperidinas , Fuso Acromático
14.
J Cell Sci ; 133(23)2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33148609

RESUMO

Temporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal and spatial control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate times to promote the progression of meiosis and development. Here, we show that changes in subcellular structures and states of the RNA-binding protein pumilio 1 (Pum1) regulate the translation of target mRNAs and progression of oocyte maturation. Pum1 was shown to bind to Mad2 (also known as Mad2l1) and cyclin B1 mRNAs, assemble highly clustered aggregates, and surround Mad2 and cyclin B1 RNA granules in mouse oocytes. These Pum1 aggregates were dissolved prior to the translational activation of target mRNAs, possibly through phosphorylation. Stabilization of Pum1 aggregates prevented the translational activation of target mRNAs and progression of oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.


Assuntos
Ciclina B1 , Proteínas Mad2/genética , Biossíntese de Proteínas , Proteínas de Ligação a RNA/química , Animais , Ciclina B1/genética , Ciclina B1/metabolismo , Meiose/genética , Camundongos , Oócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
J Math Biol ; 80(7): 2227-2255, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32335708

RESUMO

In this paper we present a novel method for finding unknown parameters for an unknown morphogen. We postulate the existence of an unknown morphogen in a given three-dimensional domain due to the spontaneous arrangement of a downstream species on the domain boundary for which data is known. Assuming a modified Helmholtz model for the morphogen and that it is produced from a single source in the domain, our method accurately estimates the source location and other model parameters. Notably, our method does not require the forward solution of the model to be computed which can often be a challenge for three-dimensional PDE model parameter fitting. Instead, an extension is made from the problem domain to an infinite domain and the analytic nature of the fundamental solution is exploited. We explore in this manuscript strategies for best conditioning the problem and rigorously explore the accuracy of the method on two test problems. Our tests focus on the effect of source location on accuracy but also the robustness of the algorithm to experimental noise.


Assuntos
Modelos Biológicos , Morfogênese/fisiologia , Algoritmos , Animais , Conceitos Matemáticos , Transdução de Sinais/fisiologia
16.
Acta Biomater ; 102: 114-126, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31756551

RESUMO

Cells in tissues are enveloped by an instructive niche made of the extracellular matrix. These instructive niches contain three general types of information: topographical, biochemical and mechanical. While the combined effects of these three factors are widely studied, the functions of each individual one has not been systematically characterised, because it is impossible to alter a single factor in a tissue microenvironment without simultaneously affecting the other two. Silica BioReplication (SBR) is a process that converts biological samples into silica, faithfully preserving the original topography at the nano-scale. We explored the use of this technique to generate inorganic replicas of intact mammalian tissues, including tendon, cartilage, skeletal muscle and spinal cord. Scanning electron and atomic force microscopy showed that the resulting replicas accurately preserved the three-dimensional ultrastructure of each tissue, while all biochemical components were eradicated by calcination. Such properties allowed the uncoupling the topographical information of a tissue microenvironment from its biochemical and mechanical components. Here, we showed that human mesenchymal stem cells (MSC) cultured on the replicas of different tissues displayed vastly different morphology and focal adhesions, suggesting that the topography of the tissue microenvironment captured by SBR could profoundly affect MSC biology. MSC cultured on tendon replica elongated and expressed tenocytes marker, while MSC on the spinal cord replica developed into spheroids that resembled neurospheres, in morphology and in the expression of neurosphere markers, and could be further differentiated into neuron-like cells. This study reveals the significance of topographical cues in a cell niche, as tissue-specific topography was sufficient in initiating and directing differentiation of MSC, despite the absence of any biochemical signals. SBR is a convenient and versatile method for capturing this topographical information, facilitating the functional characterisation of cell niches. STATEMENT OF SIGNIFICANCE: Various studies have shown that three major factors, topographical, biochemical and mechanical, in a tissue microenvironment (TME) are essential for cellular homeostasis and functions. Current experimental models are too simplistic to represent the complexity of the TME, hindering the detailed understanding of its functions. In particular, the importance each factor in a tissue microenvironment have not been individually characterised, because it is challenging to alter one of these factors without simultaneously affecting the other two. Silica bioreplication (SBR) is a process that converts biological samples into silica replicas with high structural fidelity. SBR is a convenient and versatile method for capturing this topographical information on to a biologically inert material, allowing the functional characterisation of the architecture of a TME.


Assuntos
Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/citologia , Dióxido de Silício/química , Microambiente Tumoral/fisiologia , Tendão do Calcâneo/anatomia & histologia , Animais , Cartilagem/ultraestrutura , Bovinos , Células HeLa , Humanos , Músculo Esquelético/anatomia & histologia , Compostos de Organossilício/química , Medula Espinal/anatomia & histologia , Suínos
17.
ACS Appl Mater Interfaces ; 11(21): 18988-18994, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31051073

RESUMO

Thermal scanning probe lithography (t-SPL) is a nanofabrication technique in which an immobilized thermolabile resist, such as polyphthalaldehyde (PPA), is locally vaporized by a heated atomic force microscope tip. Compared with other nanofabrication techniques, such as soft lithography and nanoimprinting lithography, t-SPL is more efficient and convenient as it does not involve time-consuming mask productions or complicated etching procedures, making it a promising candidate technique for the fast prototyping of nanoscale topographies for biological studies. Here, we established the direct use of PPA-coated surfaces as a cell culture substrate. We showed that PPA is biocompatible and that the deposition of allylamine by plasma polymerization on a silicon wafer before PPA coating can stabilize the immobilization of PPA in aqueous solutions. When seeded on PPA-coated surfaces, human mesenchymal stem cells (MSC) adhered, spread, and proliferated in a manner indistinguishable from cells cultured on glass surfaces. This allowed us to subsequently use t-SPL to generate nanotopographies for cell culture experiments. As a proof of concept, we analyzed the surface topography of bovine tendon sections, previously shown to induce morphogenesis and differentiation of MSC, by means of atomic force microscopy, and then "wrote" topographical data on PPA by means of t-SPL. The resulting substrate, matching the native tissue topography on the nanoscale, was directly used for MSC culture. The t-SPL substrate induced similar changes in cell morphology and focal adhesion formation in the MSC compared to native tendon sections, suggesting that t-SPL can rapidly generate cell culture substrates with complex and spatially accurate topographical signals. This technique may greatly accelerate the prototyping of models for the study of cell-matrix interactions.


Assuntos
Impressão , Engenharia Tecidual/métodos , Alilamina/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Gases em Plasma/farmacologia , Polimerização , Tendões/efeitos dos fármacos , Tendões/fisiologia
18.
Public Health Nutr ; 22(5): 874-881, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30394250

RESUMO

OBJECTIVE: The present study aimed to determine the relationship among food insecurity, social support and mental well-being in sub-Saharan Africa, a region presenting the highest prevalence of severe food insecurity and a critical scarcity of mental health care. DESIGN: Food insecurity was measured using the Food Insecurity Experience Scale (FIES). Social support was assessed using dichotomous indicators of perceived, foreign perceived, received, given, integrative and emotional support. The Negative and Positive Experience Indices (NEI and PEI) were used as indicators of mental well-being. Multilevel mixed-effect linear models were applied to examine the associations between mental well-being and food security status, social support and their interaction, respectively, accounting for random effects at country level and covariates.ParticipantsNationally representative adults surveyed through Gallup World Poll between 2014 and 2016 in thirty-nine sub-Saharan African countries (n 102 235). RESULTS: The prevalence of severe food insecurity was 39 %. The prevalence of social support ranged from 30 to 72 % by type. In the pooled analysis using the adjusted model, food insecurity was dose-responsively associated with increased NEI and decreased PEI. Perceived, integrative and emotional support were associated with lower NEI and higher PEI. The differences in NEI and PEI between people with and without social support were the greatest among the most severely food insecure. CONCLUSIONS: Both food insecurity and lack of social support constitute sources of vulnerability to poor mental well-being. Social support appears to modify the relationship between food security and mental well-being among those most affected by food insecurity in sub-Saharan Africa.


Assuntos
Abastecimento de Alimentos , Nível de Saúde , Saúde Mental , Apoio Social , Adulto , África Subsaariana , Depressão , Feminino , Humanos , Masculino , Inquéritos e Questionários
19.
BMC Nurs ; 17: 50, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519146

RESUMO

BACKGROUND: To adopt a healthy lifestyle is considered an essential component of nursing education. Self-rated health is a subjective assessment of health status and is consistent with objective health status. Previous studies have shown an association between self-rated health and engagement in a healthy lifestyle. Nursing students need to feel good about their subjective health status and to be able to adopt health improvements in their lifestyle before attempting to disseminate health messages to clients. The aims of this study were to compare the difference in self-rated health and health promotion lifestyle profile between senior and junior nursing students, describe correlations between self-rated health and health promotion lifestyle profile, and identify the predictors of self-rated health. METHODS: A cross-sectional descriptive survey was adopted. The study sample consisted of 314 junior and senior year nursing students from a tertiary institution. The self-reported questionnaire consisted of a single-item question to examine their self-rated health. The Health Promoting Lifestyle Profile-II: Chinese version short form (HPLP-IICR) was used to investigate the health-promoting lifestyles of the students. Descriptive statistics, Mann-Whitney U test, Chi-square test, Fisher's exact test, Spearman's correlation, and ordinal logistic regression were used to analyze the data. RESULTS: The median scores for self-rated health were 3 (Mean 3.26, IQR 3-4) and 3 (Mean 3.19, IQR 3-4) out of 5 for Year 2 and Year 5 students, respectively, with no significant difference between the two groups. The two groups of students showed no significant differences in overall score and in most subscales of the HPLP-IICR. An ordinal logistic regression showed that those students with higher health management score (OR: 1.12, 95% CI: 1.04-1.21) and who had experienced no family conflicts in the recent month than having family conflict (OR: 1.64, 95% CI: 1.01-2.66) were more likely to have higher self-rated health. CONCLUSION: Nursing education and clinical practice can undoubtedly increase the health knowledge of students, but may not lead to changes in actual health-promoting behaviours. Students with a higher health management score and no family conflicts are more likely to give a positive appraisal of their health status.

20.
J Orthop Surg Res ; 13(1): 235, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30217215

RESUMO

BACKGROUND: The purpose of this registry-based retrospective study was to investigate the risk factors related to one-year mortality in displaced intracapsular fragility hip fracture patients. METHODS: Patients were screened from the Fragility Fracture Registry. Inclusion criterion was displaced intracapsular hip fracture patients with atypical or pathological fractures excluded. One-year mortality was investigated against risk factors including age, gender, past medical history, pre-fracture mobility (PFM), pre-operation ASA grade, delayed surgery over 48 h, post-surgical complications, and length of stay at acute orthopedic ward (LOS). RESULTS: A total of 1050 patients were included for further analysis. Gross one-year mortality was 14.9%. One-year mortality was significantly higher in patients who received non-operative treatment and those who received surgery but delayed over 48 h after admission (both p <  0.001). Male gender (OR = 2.708), advanced age (OR = 1.359), higher risk ASA grades (III to V) (OR = 1.990), past history of gastrointestinal disease (OR = 1.671), and renal impairment (OR = 1.984) were related to higher one-year mortality. The mortality of patients in PFM grade 3 and LOS group 3 was significantly higher (OR = 2.240 and 1.722, respectively). CONCLUSIONS: Higher age, male gender, past gastrointestinal disease and renal impairment, ASA grade over 3, indoor confined pre-fracture ambulatory, and stay at hospital over 15 days were risk factors related to higher one-year mortality in surgically treated displaced intracapsular hip fracture patients. A multi-disciplinary approach is advised to patients identified with these risks factors and co-managed by orthopedic surgeons, geriatricians, and fracture liaison nurses.


Assuntos
Fraturas do Quadril/mortalidade , Fraturas Intra-Articulares/mortalidade , Fraturas por Osteoporose/mortalidade , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Feminino , Hong Kong , Humanos , Cápsula Articular/lesões , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco
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