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1.
Can J Cardiol ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326672

RESUMO

Hypertensive vascular disease (HVD) is a major health burden globally and is a comorbidity commonly associated with other metabolic diseases. Many factors are associated with hypertensive vascular disease including obesity, diabetes, smoking, chronic kidney disease, and sterile inflammation. Increasing evidence points to neutrophils as an important component of the chronic inflammatory response in hypertensive vascular disease. Neutrophils are abundant in the circulation and can respond rapidly upon stimulation to deploy an armament of anti-microbial effector functions. One of the outcomes of neutrophil activation is the generation of Neutrophil Extracellular Traps (NETs), a regulated extrusion of chromatin and proteases. While neutrophils and NETs are well described as components of the innate immune response to infection, recent evidence implicates them in HVD. Endothelial cell activation can trigger neutrophil adhesion, activation, and production of NETs promoting vascular dysfunction, vessel remodeling, and loss of resistance. The regulated release of NETs can be controlled by the pore-forming activities of distinct cell death pathways. The best-characterized pathways in this context are apoptosis, pyroptosis, and necroptosis. In this review, we will discuss how inflammatory cell death signaling and NET formation contribute to hypertensive disease. We also examine novel therapeutic approaches to limit NET production and their future potential as therapeutic drugs in cardiovascular disorders.

2.
Odontology ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277551

RESUMO

Regeneration of dentin and preserving pulp vitality are essential targets for vital pulp therapy. Our study aimed to evaluate a novel biomimetic pulp capping agent with increased dentin regenerative activities. To produce demineralised dentin matrix (DDM) particles, human extracted teeth were ground and treated with ethylene diamine tetra-acetic acid solution. DDM particles were added to sodium alginate and this combination was dripped into a 5% calcium chloride to obtain DDM hydrogel (DDMH). The eluants of both DDMH and mineral trioxide aggregate (MTA) were tested using an MTT assay to detect their cytotoxic effect on dental pulp stem cells (DPSC). Collagen-I (COL-I) gene expression was analysed on DPSC exposed to different dilutions of pulp capping material eluants by real-time quantitative polymerase chain reaction. Acridine orange staining was used to monitor the cell growth over the tested materials. Agar diffusion assay was utilised to test the antibacterial effect of DDMH and MTA compared to controls. MTT assay revealed that neat eluates of DDMH promoted DPSC viability. However, neat eluates of MTA were cytotoxic on DPSC after 72 h of culture. Moreover, DPSC were capable of growth and attached to the surface of DDMH, while they showed a marked reduction in their number when cultured on the MTA surface for one week, as shown by the acridine orange stain. In DPSC cultured with DDMH eluates, the COL-I gene was overexpressed compared to those cultured with MTA eluants. DDMH had significant antimicrobial activity in comparison to MTA after 24 h incubation. This in vitro study showed that DDMH could be an alternative pulp capping agent for regenerative endodontics.

3.
bioRxiv ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39282256

RESUMO

Human bronchial epithelial cells (HBECs) derived from the tracheo-bronchial regions of human airways provide an excellent in vitro model for studying pathological mechanisms and evaluating therapeutics in human airway cells. This cell population comprises a mixed population of basal cells (BCs), the predominant stem cell in airways capable of both self-renewal and functional differentiation. Despite their potential for regenerative medicine, BCs exhibit significant phenotypic variability in culture. To investigate how culture conditions influence BC phenotype and function, we expanded three independent BC isolates in three media, airway epithelial cell growth medium (AECGM), dual-SMAD inhibitor (DSI)-enriched AECGM, and Pneumacult Ex plus (PEx+). Extensive RNA sequencing, immune assays and electrical measurements revealed that PEx+ media significantly drove cell proliferation and a broad pro-inflammatory phenotype in BCs. In contrast, BCs expanded in AECGM, displayed increased expression of structural and extracellular matrix components at high passage. Whereas culture in AECGM increased expression of some cytokines at high passage, DSI suppressed inflammation altogether thus implicating TGF-ß in BC inflammatory processes. Differentiation capacity declined with time in culture irrespective of expansion media except for PLUNC expressing secretory cells that were elevated at high passage in AECGM and PEx+ suggestive of an immune modulatory role of PLUNC in BCs. These findings underscore the profound impact of media conditions on inflammatory niche and function of in vitro expanded BCs. The broad pro-inflammatory phenotype driven by PEx+ media, in particular, should be considered in the development of cell-based models for airway diseases and therapeutic application.

4.
J Evol Biol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324636

RESUMO

Eukaryotic energy production requires tight coordination between nuclear and mitochondrial gene products. Because males and females often have different energetic strategies, optimal mitonuclear coordination may be sex-specific. Previous work found evidence for sex-specific mitonuclear effects in the copepod Tigriopus californicus by comparing two parental lines and their reciprocal F1 crosses. However, an alternative hypothesis is that the patterns were driven by the parental source of nuclear alleles. Here we test this alternative hypothesis by extending the same cross to F2 hybrids, who receive both maternal and paternal nuclear alleles from F1 hybrids. Results confirm mitonuclear effects on sex ratio, with distorted ratios persisting from the F1 to F2 generations, despite reduced fitness in F2 hybrids. No sex by cross interactions were found for other phenotypic traits measured. Mitochondrial DNA content was higher in females. Both routine metabolic rate and oxidative DNA damage were lower in F2 hybrids than in parentals. The persistence of sex-specific mitonuclear effects, even in the face of F2 hybrid breakdown, attests to the magnitude of these effects, which contribute to the maintenance of within-population mitochondrial DNA polymorphisms.

5.
Cell Rep ; 43(8): 114598, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39126651

RESUMO

Endosomal Toll-like receptors (eTLRs) are essential for the sensing of non-self through RNA and DNA detection. Here, using spatiotemporal analysis of vesicular dynamics, super-resolution microscopy studies, and functional assays, we show that endomembrane defects associated with the deficiency of the small GTPase Rab27a cause delayed eTLR ligand recognition, defective early signaling, and impaired cytokine secretion. Rab27a-deficient neutrophils show retention of eTLRs in amphisomes and impaired ligand internalization. Extracellular signal-regulated kinase (ERK) signaling and ß2-integrin upregulation, early responses to TLR7 and TLR9 ligands, are defective in Rab27a deficiency. CpG-stimulated Rab27a-deficient neutrophils present increased tumor necrosis factor alpha (TNF-α) secretion and decreased secretion of a selected group of mediators, including interleukin (IL)-10. In vivo, CpG-challenged Rab27a-null mice show decreased production of type I interferons (IFNs) and IFN-γ, and the IFN-α secretion defect is confirmed in Rab27a-null plasmacytoid dendritic cells. Our findings have significant implications for immunodeficiency, inflammation, and CpG adjuvant vaccination.


Assuntos
Citocinas , Receptor Toll-Like 9 , Proteínas rab27 de Ligação ao GTP , Animais , Proteínas rab27 de Ligação ao GTP/metabolismo , Proteínas rab27 de Ligação ao GTP/genética , Camundongos , Citocinas/metabolismo , Receptor Toll-Like 9/metabolismo , Receptor Toll-Like 9/deficiência , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/deficiência , Proteínas rab de Ligação ao GTP/genética , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/deficiência , Receptor 7 Toll-Like/genética , Neutrófilos/metabolismo , Neutrófilos/imunologia , Endossomos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Necrose Tumoral alfa/metabolismo , Ácidos Nucleicos/metabolismo , Transdução de Sinais , Interferon gama/metabolismo , Glicoproteínas de Membrana
6.
AJNR Am J Neuroradiol ; 45(10): 1403-1412, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39089875

RESUMO

CSF-venous fistulas (CVFs) are a common cause of spontaneous intracranial hypotension. Despite their relatively frequent occurrence, they can be exceedingly difficult to detect on imaging. Since the initial description of CVFs in 2014, the recognition and diagnosis of this type of CSF leak has continually increased. As a result of multi-institutional efforts, a wide spectrum of imaging modalities and specialized techniques for CVF detection is now available. It is important for radiologists to be familiar with the multitude of available techniques, because each has unique advantages and drawbacks. In this article, we review the spectrum of imaging modalities available for the detection of CVFs, explain the advantages and disadvantages of each, provide typical imaging examples, and discuss provocative maneuvers that may improve the conspicuity of CVFs. Discussed modalities include conventional CT myelography, dynamic myelography, digital subtraction myelography, conebeam CT myelography, decubitus CT myelography by using conventional energy-integrating detector scanners, decubitus photon counting CT myelography, and intrathecal gadolinium MR myelography. Additional topics to be discussed include optimal patient positioning, respiratory techniques, and intrathecal pressure augmentation.


Assuntos
Hipotensão Intracraniana , Mielografia , Humanos , Mielografia/métodos , Hipotensão Intracraniana/diagnóstico por imagem , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Fístula Vascular/diagnóstico por imagem
7.
ACS Nano ; 18(33): 22220-22232, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39107108

RESUMO

Chiral molecules, a cornerstone of chemical sciences with applications ranging from pharmaceuticals to molecular electronics, come in mirror-image pairs called enantiomers. However, their synthesis often requires complex control of their molecular geometry. We propose a strategy called "electromagnetic enantiomers" for inducing chirality in molecules located within engineered nanocavities using light, eliminating the need for intricate molecular design. This approach works by exploiting the strong coupling between a nonchiral molecule and a chiral mode within a nanocavity. We provide evidence for this strong coupling through angular emission patterns verified by numerical simulations and with complementary evidence provided by luminescence lifetime measurements. In simpler terms, our hypothesis suggests that chiral properties can be conveyed on to a molecule with a suitable chromophore by placing it within a specially designed chiral nanocavity that is significantly larger (hundreds of nanometers) than the molecule itself. To demonstrate this concept, we showcase an application in display technology, achieving efficient emission of circularly polarized light from a nonchiral molecule. The electromagnetic enantiomer concept offers a simpler approach to chiral control, potentially opening doors for asymmetric synthesis.

8.
Cell Rep ; 43(8): 114547, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39083377

RESUMO

During chronic infection, virus-specific CD8+ cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This "exhaustion" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Pdcd1 alleles dissociate from transcriptionally repressive chromatin domains (lamin B) in virus-specific exhausted CTLs but not in naive or effector CTLs. Relative to naive CTLs, nuclear positioning and Pdcd1-lamina dissociation in exhausted CTLs reflect loss of Pdcd1 promoter methylation and greater PD-1 upregulation, although a direct correlation is not observed in effector cells, 8 days post-infection. Genetic deletion of B lymphocyte-induced maturation protein 1 (Blimp-1) enhances Pdcd1-lamina dissociation in effector CTLs, suggesting that Blimp-1 contributes to maintaining Pdcd1 localization to repressive lamina. Our results identify mechanisms governing Pdcd1 subnuclear localization and the broader role of chromatin dynamics in T cell exhaustion.


Assuntos
Coriomeningite Linfocítica , Vírus da Coriomeningite Linfocítica , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1 , Linfócitos T Citotóxicos , Animais , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/genética , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Núcleo Celular/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Doença Crônica , Regiões Promotoras Genéticas/genética , Loci Gênicos
9.
Am Psychol ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052356

RESUMO

Self-determination theory's (SDT) dual process model claims that parental autonomy support relates positively to child well-being, while psychologically controlling parenting is linked positively to child ill-being. We tested these claims using a combination of one-stage and univariate meta-analytic structural equation modeling with moderation (k = 238; n = 1,040, N = 126,423). In the univariate models, parental autonomy support was linked positively with child well-being, r = 0.30, 95% CI [0.26, 0.33], whereas parental psychological control was positively linked with child ill-being, r = 0.26, 95% CI [0.23, 0.28]. Consistent with SDT's dual process model, the one-stage model that controlled for the intercorrelations between predictors showed that parental autonomy support and psychological control had distinct links to child wellness outcomes. Parental autonomy support was linked positively with child well-being, even when accounting for psychological control, r = 0.26, 95% CI [0.20, 0.31], and parental psychological control was positively linked to child ill-being, controlling for autonomy support, r = 0.20, 95% CI [0.17, 0.23]. Crucially, the beneficial effects of parental autonomy support and the costs of psychological control applied across regions, degrees of national individualism and cultural hierarchy, as well as child developmental periods and sexes. These results help move the field beyond debates about whether autonomy is beneficial toward questions about manifestations of autonomy across groups and variations in its optimal support. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

10.
Proc Natl Acad Sci U S A ; 121(30): e2408109121, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39028694

RESUMO

The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell-intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic.


Assuntos
COVID-19 , Pulmão , Organoides , SARS-CoV-2 , Internalização do Vírus , Humanos , SARS-CoV-2/fisiologia , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/virologia , Pulmão/virologia , Pulmão/imunologia , Pulmão/patologia , Organoides/virologia , Tratamento Farmacológico da COVID-19 , Células-Tronco Pluripotentes Induzidas/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Inflamação , Citocinas/metabolismo , Apoptose
11.
Pain ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39073407

RESUMO

ABSTRACT: Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Microglia display similar morphological responses in the spinal cord after peripheral nerve injury (PNI). Consistent with this observation, functional studies have suggested that microglia activated by opioids or PNI engage common molecular mechanisms to induce hypersensitivity. In this article, we conducted deep RNA sequencing (RNA-seq) and morphological analysis of spinal cord microglia in male mice to comprehensively interrogate transcriptional states and mechanistic commonality between multiple models of OIH and PNI. After PNI, we identify an early proliferative transcriptional event across models that precedes the upregulation of histological markers of microglial activation. However, we found no proliferative transcriptional response associated with opioid-induced microglial activation, consistent with histological data, indicating that the number of microglia remains stable during morphine treatment, whereas their morphological response differs from PNI models. Collectively, these results establish the diversity of pain-associated microglial transcriptomic responses and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other central nervous system pathologies.

12.
Vaccines (Basel) ; 12(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38932386

RESUMO

It is important to understand real-world BNT162b2 COVID-19 vaccine effectiveness (VE), especially among racial and ethnic minority groups. We performed a test-negative case-control study to measure BNT162b2 COVID-19 VE in the prevention of COVID-19-associated acute respiratory illness (ARI) hospitalizations at two Atlanta hospitals from May 2021-January 2023 and adjusted for potential confounders by multivariate analysis. Among 5139 eligible adults with ARI, 2763 (53.8%) were enrolled, and 1571 (64.5%) were included in the BNT162b2 analysis. The median age was 58 years (IQR, 44-68), 889 (56.6%) were female, 1034 (65.8%) were African American, 359 (22.9%) were White, 56 (3.6%) were Hispanic ethnicity, 645 (41.1%) were SARS-CoV-2-positive, 412 (26.2%) were vaccinated with a primary series, and 273 (17.4%) had received ≥1 booster of BNT162b2. The overall adjusted VE of the BNT162b2 primary series was 58.5% (95% CI 46.0, 68.1), while the adjusted VE of ≥1 booster was 78.9% (95% CI 70.0, 85.1). The adjusted overall VE of primary series for African American/Black individuals was 64.0% (95% CI 49.9, 74.1) and 82.7% (95% CI 71.9, 89.4) in those who received ≥1 booster. When analysis was limited to the period of Omicron predominance, overall VE of the primary series decreased with widened confidence intervals (24.5%, 95% CI -4.5, 45.4%), while VE of ≥1 booster was maintained at 60.9% (95% CI 42.0, 73.6). BNT162b2 primary series and booster vaccination provided protection against COVID-19-associated ARI hospitalization among a predominantly African American population.

13.
Proc Natl Acad Sci U S A ; 121(24): e2321267121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38838014

RESUMO

Mitochondria perform an array of functions, many of which involve interactions with gene products encoded by the nucleus. These mitochondrial functions, particularly those involving energy production, can be expected to differ between sexes and across ages. Here, we measured mitochondrial effects on sex- and age-specific gene expression in parental and reciprocal F1 hybrids between allopatric populations of Tigriopus californicus with over 20% mitochondrial DNA divergence. Because the species lacks sex chromosomes, sex-biased mitochondrial effects are not confounded by the effects of sex chromosomes. Results revealed pervasive sex differences in mitochondrial effects, including effects on energetics and aging involving nuclear interactions throughout the genome. Using single-individual RNA sequencing, sex differences were found to explain more than 80% of the variance in gene expression. Males had higher expression of mitochondrial genes and mitochondrially targeted proteins (MTPs) involved in oxidative phosphorylation (OXPHOS), while females had elevated expression of non-OXPHOS MTPs, indicating strongly sex-dimorphic energy metabolism at the whole organism level. Comparison of reciprocal F1 hybrids allowed insights into the nature of mito-nuclear interactions, showing both mitochondrial effects on nuclear expression, and nuclear effects on mitochondrial expression. While based on a small set of crosses, sex-specific increases in mitochondrial expression with age were associated with longer life. Network analyses identified nuclear components of strong mito-nuclear interactions and found them to be sexually dimorphic. These results highlight the profound impact of mitochondria and mito-nuclear interactions on sex- and age-specific gene expression.


Assuntos
Mitocôndrias , Cromossomos Sexuais , Animais , Feminino , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Cromossomos Sexuais/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Fosforilação Oxidativa , Caracteres Sexuais , DNA Mitocondrial/genética , Núcleo Celular/metabolismo , Núcleo Celular/genética , Regulação da Expressão Gênica , Metabolismo Energético/genética
14.
BMC Psychol ; 12(1): 351, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879510

RESUMO

BACKGROUND: The literature for assessing online and offline shopping behaviours that are linked to intelligent robotic goods and services is inadequate. In this study, we applied the Theory of Planned Behaviour model for guidance regarding how consumer behaviour affects their purchase intentions for intelligent robotic goods and services. METHODS: Data from 408 respondents were gathered through an online questionnaire binned into Online and Overall Shoppers, and analysed using SPSS, AMOS, and Covariance-Based Structural Equation Modelling software to evaluate the appropriateness of the measurements and to confirm data reliability, convergence, divergence, and validity. These tools were also used to track and test hypothesized relationships between the variables and model constructs used in this study. RESULTS AND CONCLUSIONS: The overarching outcomes from the data analyses indicated the Ease of Usage, Brand Perception, and Product Pricing variables causally impacted the TPB model constructs, namely Attitude, Subjective Norms, and Perceived Behaviour Control for the two populations tested with respect to their intention to purchase intelligent robotic goods and services. The reliability measurements for Ease of Usage, Brand Perception, and Product Pricing are discussed. The results are important for companies and future investors because opportunities to study the complex relationships that ultimately drive consumer behaviour and their intention to purchase intelligent robotic goods and services are provided.


Assuntos
Comportamento do Consumidor , Intenção , Teoria Psicológica , Robótica , Humanos , Comportamento do Consumidor/estatística & dados numéricos , Masculino , Feminino , Adulto , Taiwan , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem , Teoria do Comportamento Planejado
15.
Dent Mater ; 40(8): 1252-1258, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876829

RESUMO

OBJECTIVES: Quality control testing of dental materials requires a standard to enable the generation of reproducible and comparable data. Currently there are no standards for testing materials used for vital pulp therapy. The aim of this study was to develop a new standard to evaluate solubility of pulp preservation materials. METHODS: The solubility of three materials used for vital pulp therapy: Biodentine, TheraCal and Activa was evaluated using two international standards for dental materials ISO 4049:2019 (S1) and ISO 6876:2012 (S2). For both standards, a modified methodology was evaluated. This included changing the volume of the solution used (S1M, S2M), using Dulbecco's modified eagle medium (DMEM) as an alternative to water (S1D, S2D) and periodic solution change for the ISO 4049 method (S1P, S1MP). Materials were characterised before and after completion of solubility test using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. RESULTS: The test materials exhibited different solubility values depending on the methodology used. Biodentine exhibited significantly lower solubility when lower volumes of solution were used when tested using both ISO methods (p ≤ 0.05). TheraCal and Activa showed negative solubility values after desiccation when tested using ISO 4049:2019. The Biodentine exhibited changes in its microstructure which was dependent on the method used to test solubility. CONCLUSIONS: The solubility values obtained were dependent on the method used. It is thus important to use methods that replicate the clinical environment for meaningful evaluations.


Assuntos
Compostos de Cálcio , Teste de Materiais , Microscopia Eletrônica de Varredura , Silicatos , Solubilidade , Difração de Raios X , Silicatos/química , Compostos de Cálcio/química , Materiais Dentários/química , Compostos de Alumínio/química , Agentes de Capeamento da Polpa Dentária e Pulpectomia/química , Óxidos/química , Combinação de Medicamentos
16.
Open Forum Infect Dis ; 11(6): ofae072, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38887482

RESUMO

Invasive candidiasis is a rising global health threat with increasing incidence, persistently high mortality, and diminishing treatment options. Antifungal resistance has rapidly emerged and spread, with multidrug-resistant species deemed an urgent and serious threat. While acknowledging the key role of antifungal stewardship and infection control in curbing spread, we examine the role of antifungal monotherapy in driving resistance and the potential for combination therapy to prevent stress adaptation and emergence of drug resistance. In addition to its role in mitigating resistance, combination treatment may improve drug penetration, expedite fungal clearance, and allow lower, less toxic doses of individual drugs to be used. A growing body of laboratory-based evidence suggests that antifungal combinations can yield synergistic activity against Candida spp., including against frequently multidrug-resistant Candida auris. It is imperative to test these combinations in clinical trials, incorporating resistance end points as a marker of success.

17.
Acta Paediatr ; 113(9): 2031-2036, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38808465

RESUMO

AIM: Sudden unexpected postnatal collapse is a life-threatening event and may occur in any newborn infant. Safe skin-to-skin contact, and awareness of sudden unexpected postnatal collapse are key to its prevention. The aim of this study was to survey the presence of skin-to-skin contact and/or sudden unexpected postnatal collapse protocols in the 70 perinatal centres in the Netherlands. METHODS: We performed a survey among Dutch paediatricians to examine the safe skin-to-skin contact and sudden unexpected postnatal collapse protocols. RESULTS: We received data from 59/70 (85%) perinatal centres. At least one case of sudden unexpected postnatal collapse was reported in 35/59 (59%) of these centres. Nearly half the centres had safe skin-to-skin contact and/or sudden unexpected postnatal collapse protocols. Ultimately, 16 protocols were available for analysis. They showed considerable differences in the type of perinatal care provided. Most protocols lacked recently published insights on safe skin-to-skin contact. Besides, protocols failed to incorporate awareness of and knowledge on how to prevent sudden unexpected postnatal collapse. CONCLUSION: This study underlines the importance of drawing up uniform, multidisciplinary guidelines containing recommendations for the prevention of sudden unexpected postnatal collapse in the Netherlands.


Assuntos
Guias de Prática Clínica como Assunto , Morte Súbita do Lactente , Humanos , Recém-Nascido , Países Baixos , Morte Súbita do Lactente/prevenção & controle , Método Canguru , Fidelidade a Diretrizes/estatística & dados numéricos
18.
J Evid Based Integr Med ; 29: 2515690X241251558, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689490

RESUMO

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p < .05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice.


Assuntos
Clorofórmio , Fígado , Carcinoma Hepatocelular/induzido quimicamente , Raízes de Plantas/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Clausena , Dietilaminas/toxicidade , Antineoplásicos Fitogênicos/farmacologia
19.
Nano Lett ; 24(22): 6813-6820, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38781191

RESUMO

Spintronic devices incorporating magnetic skyrmions have attracted significant interest recently. Such devices traditionally focus on controlling magnetic textures in 2D thin films. However, enhanced performance of spintronic properties through the exploitation of higher dimensionalities motivates the investigation of variable-thickness skyrmion devices. We report the demonstration of a skyrmion injection mechanism that utilizes charge currents to drive skyrmions across a thickness step and, consequently, a metastability barrier. Our measurements show that under certain temperature and field conditions skyrmions can be reversibly injected from a thin region of an FeGe lamella, where they exist as an equilibrium state, into a thicker region, where they can only persist as a metastable state. This injection is achieved with a current density of 3 × 108 A m-2, nearly 3 orders of magnitude lower than required to move magnetic domain walls. This highlights the possibility to use such an element as a skyrmion source/drain within future spintronic devices.

20.
Brain Res ; 1838: 148994, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38729331

RESUMO

PTZ kindling induces oxidative stress, neuronal cell degeneration, and neurobehavioral alterations in rodents that mimic neuropsychiatric comorbidities of epilepsy, which could be initiated or aggravated by some antiepileptic drugs. Here, we investigated the effects of the methanol extract of Ficus platyphylla (FP) on severity scores for seizures, neuronal cell degeneration, and neurobehavioral alterations in rats kindled with pentylenetetrazole (PTZ) and probed the involvement of oxidative stress in these ameliorative effects of FP. FP (50 and 100 mg/kg, p.o.) ameliorated seizure severity, neuronal cell degeneration, depressive behaviors, cognitive dysfunctions, and oxidative stress in rats kindled with PTZ (42.5 mg/kg, i.p.). The findings from this study give additional insights into the potential values of FP in the treatment of persistent epilepsy and major neuropsychiatric comorbidities via modulation of oxidative stress.


Assuntos
Anticonvulsivantes , Ficus , Excitação Neurológica , Estresse Oxidativo , Pentilenotetrazol , Extratos Vegetais , Convulsões , Animais , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Excitação Neurológica/efeitos dos fármacos , Masculino , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Convulsões/induzido quimicamente , Ratos , Anticonvulsivantes/farmacologia , Ratos Wistar , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente
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