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1.
J Infect Dis ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839048

RESUMO

BACKGROUND: Some individuals may not retain adequate immunity against measles and rubella years after two doses of measles, mumps, and rubella (MMR) vaccination due to vaccine failure. This study aimed to investigate the rates of vaccine failure and seroconversion by administering an MMR booster to young adults. METHODS: We first assessed measles and rubella antibody levels using the Luminex multiplex assay, VIDAS IgG assay, and plaque reduction neutralization test (PRNT) among individuals aged 18-30 years old who had received two doses of MMR vaccine. Participants with low measles and/or rubella antibody levels as confirmed by VIDAS received an MMR booster. Antibody levels were measured at 1-month post-booster. RESULTS: Among 791 participants, the measles and rubella seroprevalence rates were 94.7% (95% CI: 92.9%-96.0%) and 97.3% (95% CI: 96.0%-98.3%), respectively. Lower seroprevalence rates were observed among older participants. 113 participants who received an MMR booster acquired higher measles and rubella antibody levels at 1-month post-booster compared to baseline. CONCLUSIONS: Although measles and rubella vaccine failures were observed among 5.3% and 2.7% of young adults, respectively, an MMR booster triggered a significant antibody response.

2.
Biomed Opt Express ; 15(5): 3492-3506, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38855686

RESUMO

This study introduces a cutting-edge fiber-optic dosimetry (FOD) sensor designed for measuring radiation in biological settings. The accuracy and precision of dosimeters for small animals, particularly prolonged exposure to nonuniform radiation fields, are always challenging. A state-of-the-art in-vivo dosimeter utilizing glass-encapsulated Thermoluminescence cylindrical detector (TLD) was introduced. The FODs are implanted into the rat during a prolonged irradiation scenario involving 137Cs where the rat has the freedom to move within a heterogeneous radiation domain. The implantation surgery was verified with X-ray computed tomography (CT) in addition to biochemical and pathological tests to assess the biocompatibility of FOD in vivo. A versatile FOD is designed for industrial and medical fields, which demand accurate and resilient radiation dosimeters. The dose measurements are associated with precise two-dimensional (2D) radiation distribution imaging. Three cylindrical FODs and three standards TLD_100 for each rat were tested. The measurements of peak irradiation before and after exposure reveal greater stability and superior sensitivity when compared to standard thermo-luminescence detectors in an in-vivo animal test. To the best of our knowledge, FOD testing on live animals is presented for the first time in this paper. Regarding the safety and biocompatibility of FOD, no morphological signs with any kind of inflammation or sensitivity toward the FOD material have been remarked. Moreover, with the current FOD, there is no oedema between the epidermal, dermal, and subdermal sections at the site of implantation. The results also show the stable levels of white blood cells (lymphocytes, granulocytes, MID) as blood inflammatory markers before surgery and at the time of extraction of the implanted dosimeters, thus confirming the biocompatibility for each optical fiber cylinder dosimeter. As a result, the new dosimeters have excellent biocompatibility in living tissues and have 100% accurate reusability intensity of the delivered radiation doses compared to TLD_100 which demonstrated a 45% reduction in its intensity accuracy.

3.
Arthritis Res Ther ; 26(1): 99, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741185

RESUMO

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.


Assuntos
Lúpus Eritematoso Sistêmico , Transcriptoma , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Humanos , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos , Leucócitos Mononucleares/metabolismo , Mapas de Interação de Proteínas/genética
4.
Health Place ; 88: 103259, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776750

RESUMO

There has been a plethora of studies on urbanization and older adults, and more recent ones on how older adults adapt to this process with their cognitive competence. Yet it has been unclear about the relationship between them, like how the level and rate of urbanization affect the cognitive function among older adults. This study sourced, formed, and analyzed a set of geospatial big datasets from different sources, such as the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data, and the NPP/VIIRS nighttime light (NTL) data. Results showed a generally negative linear association between the rate of urbanization and cognitive performance among older adults in China. The "U" shaped non-linear relationship between urbanization level and cognitive function, as well as the tipping point, were identified. At the same time, it should be noted that mediators such as education, physical activity, social activity, and community elderly service might be able to mitigate these negative associations. Furthermore, older adults living in eastern regions or urban areas appeared to have better cognitive function than those living in mid-western regions or rural areas in China. The findings also pointed to the importance of focusing on older adults with poor cognitive health status in rapidly urbanizing areas.


Assuntos
Cognição , Urbanização , Humanos , China/epidemiologia , Idoso , Masculino , Feminino , Estudos Longitudinais , Idoso de 80 Anos ou mais , Análise Espacial , População Rural/estatística & dados numéricos , Pessoa de Meia-Idade , População Urbana
5.
Innov Aging ; 8(4): igad140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628819

RESUMO

Background and Objectives: Because of the global population aging, more informal carers become older adults. In Nigeria, the African country with the largest population of adults aged 60 years and older, self-construal rooted in the African collectivist philosophy generally shapes informal caregiving for older adults. However, there is a general paucity of studies on older adults' informal caregiving roles, particularly about their motivations for caregiving. This study explored older adults' motives for informal caregiving to their care recipients in urban Southeast Nigeria. Research Design and Methods: This study adopted a hermeneutic phenomenological research design. In-depth interviews were conducted with 30 purposively selected older adults aged 54-88 who were the primary carers of other older adults in the family and community. The collected data were analyzed using van Manen's thematic analysis method, using QSR NVivo 12 software. Results: A total of 4 main themes emerged from the participants' responses: reciprocity of kindness, altruism, a sense of moral responsibility, and eagerness for peaceful longevity. The findings generally showed that religion and culture were the latent factors ingrained in these motivations for informal caregiving. Discussion and Implications: Although the African philosophy emphasizes altruism, reciprocity seems more prominent in specific traditional African communities, as observed in Southeast Nigeria. It serves as a means to prioritize family members' needs. The findings indicate the need for the government to establish sustainable programs and policies that support older people in their caregiving role. Doing so will enable carers to derive psychosocial gains from informal caregiving and sustain the caregiving culture of Nigeria.

6.
Eur J Pharmacol ; 972: 176559, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38588768

RESUMO

This study aimed to assess whether brief recall of methamphetamine (MA) memory, when combined with ketamine (KE) treatment, may prevent stress-primed MA memory reinstatement. Combining 3-min recall and KE facilitated MA memory extinction and resistance to subsequent stress-primed reinstatement. Such combination also produced glutamate metabotropic receptor 5 (mGluR5) upregulation in animals' medial prefrontal cortex (mPFC) γ-amino-butyric acid (GABA) neuron. Accordingly, chemogenetic methods were employed to bi-directionally modulate mPFC GABA activity. Following brief recall and KE-produced MA memory extinction, intra-mPFC mDlx-Gi-coupled-human-muscarinic-receptor 4 (hM4Di)-infused mice receiving compound 21 (C21) treatment showed eminent stress-primed reinstatement, while their GABA mGluR5 expression seemed to be unaltered. Intra-mPFC mDlx-Gq-coupled-human-muscarinic-receptor 3 (hM3Dq)-infused mice undergoing C21 treatment displayed MA memory extinction and resistance to stress-provoked reinstatement. These results suggest that combining a brief recall and KE treatment and exciting mPFC GABA neuron may facilitate MA memory extinction and resistance to stress-primed recall. mPFC GABA neuronal activity plays a role in mediating brief recall/KE-produced effects on curbing the stress-provoked MA seeking.


Assuntos
Extinção Psicológica , Ketamina , Rememoração Mental , Metanfetamina , Córtex Pré-Frontal , Receptor de Glutamato Metabotrópico 5 , Estresse Psicológico , Animais , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Metanfetamina/farmacologia , Ketamina/farmacologia , Masculino , Camundongos , Rememoração Mental/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/psicologia , Receptor de Glutamato Metabotrópico 5/metabolismo , Extinção Psicológica/efeitos dos fármacos , Memória/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Camundongos Endogâmicos C57BL
7.
Int J Antimicrob Agents ; 63(1): 107020, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37898365

RESUMO

OBJECTIVES: This study aimed to evaluate the effect of administering nirmatrelvir/ritonavir and molnupiravir before hospitalisation on subsequent critical illness among patients with COVID-19 pneumonia. METHODS: This retrospective cohort study included patients with COVID-19 pneumonia who required hospitalisation between 1 January 1 2022 and 31 August 2022. The primary outcomes were the development of critical illness, including intensive care unit admission, use of mechanical ventilation, or mortality. A multivariate logistic regression analysis was conducted to assess the varying risks of critical illness and mortality. A total of 1,011 COVID-19 patients were analysed. Among them, 304 (30.1%) received molnupiravir and 131 (13.0%) received nirmatrelvir/ritonavir before hospitalisation. RESULTS: There were significant reductions for critical illness (adjusted odds ratio 0.29, 95% confidence interval 0.21-0.39, P < 0.001) and mortality (adjusted odds ratio 0.40, 95% confidence interval 0.27-0.59, P < 0.001) in patients receiving oral antivirals compared with those who did not. No significant differences in critical illness were observed between molnupiravir and nirmatrelvir/ritonavir. The combination of COVID-19 vaccines and oral antivirals can further reduce the risk of critical illness in high-risk populations. CONCLUSION: Administering molnupiravir and nirmatrelvir/ritonavir before hospitalisation reduced the risk of COVID-19 patients with moderate to severe pneumonia progressing to critical illness and mortality.


Assuntos
COVID-19 , Citidina/análogos & derivados , Hidroxilaminas , Lactamas , Leucina , Nitrilas , Prolina , Humanos , Vacinas contra COVID-19 , Ritonavir/uso terapêutico , Estado Terminal , Estudos Retrospectivos , Hospitalização , Antivirais/uso terapêutico
9.
World J Pediatr ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085470

RESUMO

BACKGROUND: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents. METHODS: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. RESULTS: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. CONCLUSION: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38141203

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

11.
Nat Commun ; 14(1): 7213, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938215

RESUMO

The canonical studies on Mie scattering unravel strong electric/magnetic optical responses in nanostructures, laying foundation for emerging meta-photonic applications. Conventionally, the morphology-sensitive resonances hinge on the normalized frequency, i.e. particle size over wavelength, but non-paraxial incidence symmetry is overlooked. Here, through confocal reflection microscopy with a tight focus scanning over silicon nanostructures, the scattering point spread functions unveil distinctive spatial patterns featuring that linear scattering efficiency is maximal when the focus is misaligned. The underlying physical mechanism is the excitation of higher-order multipolar modes, not accessible by plane wave irradiation, via displacement resonance, which showcases a significant reduction of nonlinear response threshold, sign flip in all-optical switching, and spatial resolution enhancement. Our result fundamentally extends the century-old light scattering theory, and suggests new dimensions to tailor Mie resonances.

12.
Kidney Int Rep ; 8(11): 2356-2367, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38025215

RESUMO

Introduction: Patients with severe kidney diseases are at risk of complications from COVID-19; however, little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated 3-dose primary series of COVID-19 vaccination among 59 pediatric patients with chronic kidney disease (CKD) (mean age 12.9 years; 30 male) with or without immunosuppression, dialysis, or kidney transplant. Dosage was 0.1 ml BNT162b2 to those aged 5 to 11 years, and 0.3 ml BNT162b2 to those aged 11 to 18 years. Results: Three doses of either vaccine type elicited significant antibody responses that included spike receptor-binding domain (S-RBD) IgG (90.5%-93.8% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6%-79.3%). There were notable T cell responses. Weaker neutralization responses were observed among those on immunosuppression, especially those receiving higher number of immunosuppressants or on mycophenolate mofetil. Neutralization was reduced against Omicron BA.1 compared to wild type (WT, i.e., ancestral) (post-dose 3 sVNT% level; 82.7% vs. 27.4%; P < 0.0001). However, the T cell response against Omicron BA.1 was preserved, which likely confers protection against severe COVID-19. Infected patients exhibited hybrid immunity after vaccination, as evidenced by the higher Omicron BA.1 neutralization response among these infected patients who received 2 doses compared with those who were uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusion: An accelerated 3-dose primary series with BNT162b2 is immunogenic and safe in young children and adolescents with kidney diseases.

13.
Curr Issues Mol Biol ; 45(10): 8309-8320, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37886967

RESUMO

Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor in adults. Despite the advances in GBM treatment, outcomes remain poor, with a 2-year survival rate of less than 5%. Hyperbaric oxygen (HBO) therapy is an intermittent, high-concentration, short-term oxygen therapy used to increase cellular oxygen content. In this study, we evaluated the effects of HBO therapy, alone or combined with other treatment modalities, on GBM in vitro and in vivo. In the in vitro analysis, we used a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess the effects of HBO therapy alone, a colony formation assay to analyze the effects of HBO therapy combined with radiotherapy and with temozolomide (TMZ), and a neurosphere assay to assess GBM stemness. In the in vivo analysis, we used immunohistochemical staining and in vivo bioluminescence imaging to assess GBM stemness and the therapeutic effect of HBO therapy alone or combined with TMZ or radiotherapy, respectively. HBO therapy did not affect GBM cell viability, but it did reduce the analyzed tumors' ability to form cancer stem cells. In addition, HBO therapy increased GBM sensitivity to TMZ and radiotherapy both in vitro and in vivo. HBO therapy did not enhance tumor growth and exhibited adjuvant effects to chemotherapy and radiotherapy through inhibiting GBM stemness. In conclusion, HBO therapy shows promise as an adjuvant treatment for GBM by reducing cancer stem cell formation and enhancing sensitivity to chemotherapy and radiotherapy.

15.
Front Immunol ; 14: 1267933, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37809096

RESUMO

Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10-20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS.


Assuntos
Síndromes Periódicas Associadas à Criopirina , Criança , Humanos , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Estudos de Coortes , Inflamassomos , China , Prednisolona/uso terapêutico
16.
J Extracell Vesicles ; 12(9): e12360, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37654012

RESUMO

γδ-T cells are innate-like T cells with dual antitumor activities. They can directly eradicate tumor cells and function as immunostimulatory cells to promote antitumor immunity. Previous studies have demonstrated that small extracellular vesicles (EVs) derived from γδ-T cells (γδ-T-EVs) inherited the dual antitumor activities from their parental cells. However, it remains unknown whether γδ-T-EVs can be designed as tumors vaccine to improve therapeutic efficacy. Here, we found that γδ-T-EVs had immune adjuvant effects on antigen-presenting cells, as revealed by enhanced expression of antigen-presenting and co-stimulatory molecules, secretion of pro-inflammatory cytokines and antigen-presenting ability of DCs after γδ-T-EVs treatment. The γδ-T-EVs-based vaccine was designed by loading tumor-associated antigens (TAAs) into γδ-T-EVs. Compared with γδ-T-EVs, the γδ-T-EVs-based vaccine effectively promoted more tumor-specific T-cell responses. In addition, the vaccine regimen preserved direct antitumor effects and induced tumor cell apoptosis. Interestingly, the allogeneic γδ-T-EVs-based vaccine showed comparable preventive and therapeutic antitumor effects to their autologous counterparts, indicating a better way of centralization and standardization in clinical practice. Furthermore, the allogeneic γδ-T-EVs-based vaccine displayed advantages over the DC-EVs-based vaccine through their dual antitumor activities. This study provides a proof-of-concept for using the allogeneic γδ-T-EVs-based vaccine in cancer control.


Assuntos
Vacinas Anticâncer , Vesículas Extracelulares , Adjuvantes Imunológicos , Apoptose , Citocinas
17.
Cell Biosci ; 13(1): 168, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700376

RESUMO

BACKGROUND: A motor unit (MU) is formed by a single alpha motor neuron (MN) and the muscle fibers it innervates. The MU is essential for all voluntary movements. Functional deficits in the MU result in neuromuscular disorders (NMDs). The pathological mechanisms underlying most NMDs remain poorly understood, in part due to the lack of in vitro models that can comprehensively recapitulate multistage intercellular interactions and physiological function of the MU. RESULTS: We have designed a novel three-dimensional (3D) bilayer hydrogel tri-culture system where architecturally organized MUs can form in vitro. A sequential co-culture procedure using the three cell types of a MU, MN, myoblast, and Schwann cell was designed to construct a co-differentiating tri-culture on a bilayer hydrogel matrix. We utilized a µ-molded hydrogel with an additional Matrigel layer to form the bilayer hydrogel device. The µ-molded hydrogel layer provides the topological cues for myoblast differentiation. The Matrigel layer, with embedded Schwann cells, not only separates the MNs from myoblasts but also provides a proper micro-environment for MU development. The completed model shows key MU features including an organized MU structure, myelinated nerves, aligned myotubes innervated on clustered neuromuscular junctions (NMJs), MN-driven myotube contractions, and increases in cytosolic Ca2+ upon stimulation. CONCLUSIONS: This organized and functional in vitro MU model provides an opportunity to study pathological events involved in NMDs and peripheral neuropathies, and can serve as a platform for physiological and pharmacological studies such as modeling and drug screening. Technically, the rational of this 3D bilayer hydrogel co-culture system exploits multiple distinct properties of hydrogels, facilitating effective and efficient co-culturing of diverse cell types for tissue engineering.

18.
Eur J Clin Nutr ; 77(12): 1113-1129, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37661229

RESUMO

BACKGROUND: There is still paucity on the effects of dietary and supplemental fatty acid on non-alcoholic fatty liver disease (NAFLD). The aim of this review is to systematically review and summarise the effect of fatty acids intake on liver-related outcomes in adult patients with NAFLD. METHODS: The review was conducted using Cochrane CENTRAL Library, Scopus, Embase, MEDLINE, PubMed, and Web of Science. A total of 2786 records were identified, and of these, 36 studies (31 were randomised control trials (RCTs), and 5 were case-control studies) were included. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool and Joanna Briggs Institute checklists. RESULTS: Of 36 articles, 79% of RCTs and 66% of case-control studies had a low risk of bias. Potential heterogeneity has been observed in assessment of liver-related outcomes. According to the RCTs, there was moderate evidence (3/6 studies) that a diet characterised by a high MUFA, PUFA and low SFA showed reduced liver fat and stiffness. The using of culinary fats that are high in MUFA (4/6 studies) reduces liver steatosis. n-3 PUFA supplementation in combination with a hypocaloric or heart healthy diet with a low SFA improved liver enzyme level (5/14 studies) and steatosis score (3/14 studies). CONCLUSIONS: Effects on NAFLD parameters, including liver fat content (assessed via magnetic resonance imaging/spectroscopy), stiffness and steatosis score (assessed by ultrasonography), were primarily related to fatty acid composition independent of energy intake. Further investigation is needed to determine the mechanism of specific fatty acid on the accumulation of liver fat.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Ácidos Graxos , Estudos de Casos e Controles
19.
3D Print Addit Manuf ; 10(4): 732-748, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37609594

RESUMO

Laser powder bed fusion (LPBF) provides a rapid and versatile approach for producing parts with complex geometries. However, many parts with intricate geometries have overhang structures, which are not easily fabricated by using LPBF and are often downgraded by staircase effects, warpage, cracks, and dross formation. Thus, the present study proposes a combined numerical and experimental approach for determining the optimal settings of the laser power and scanning speed that minimize the surface roughness and maximize the density of Inconel 718 LPBF overhang structures. In the proposed approach, the heat transfer simulations are employed to determine the melt pool depth, the melt pool length, and the solid cooling rate within the feasible input space of laser power and scanning speed combinations. Notably, the simulations take account of both the difference in the material properties of the solid and powder materials, respectively, and the variation of the laser absorptivity in the depth direction of the powder layer. The simulation results are then used to train artificial neural networks for predicting the melt pool depth for 3600 combinations of the laser power and scanning speed within the input space. The resulting processing maps are screened in accordance with three quality criteria (namely the melt pool depth, the melt pool length, and the solid cooling rate) to determine the optimal processing region, which improves the surface roughness. The feasibility of the proposed approach is demonstrated by fabricating 10 × 10 and 20 × 20 mm2 horizontal overhang structures using parameter settings chosen from the optimal processing map. It shows that the optimal processing conditions result in a low surface roughness and a maximum density of 99.78%.

20.
Int J Qual Stud Health Well-being ; 18(1): 2250093, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37652707

RESUMO

The aim of this study was to explore the self and identity perspectives among Chinese adolescents with severe mental illness (SMI), with a focus on their illness experience and subjective meaning of a formal diagnosis. Thirty-one Chinese adolescents were interviewed and the interview data were analysed strictly according to principles suggested by the constructivist grounded theory approach. Five theoretical codes emerged in this study, including changes of personal values and beliefs, accumulated persistent developmental challenges and personal stresses, ineffective coping strategies and development, symptoms and development of mental illness, and changed perceptions and understandings of self. A proposed model of "The dynamic interactions of Chinese adolescents' identity and mental illness", was constructed and visualized. The results revealed that adolescents' identity formation is a fluctuating and non-linear process, but tends to be predominantly negative. The negative self, as informed by long-term ineffective coping with accumulated persistent developmental challenges and stressful events, develops towards a more serious status of negative identity and contributes to relapse symptoms, although this impact occurs variably with perceived personal characteristics. Besides, some participants who had achieved a state of "Buddha-like numbness" made a conscious decision to live a seemingly normal life while coexisting with their illness. The study also highlighted the positive aspects of identity formation that can arise from the experience of illness, including an enhanced sense of realism and increased empathy. Our findings will imply much the need for person-centred treatment plan and services that take into account of individual situations.


Assuntos
População do Leste Asiático , Transtornos Mentais , Autoimagem , Adolescente , Humanos , Adaptação Psicológica , População do Leste Asiático/psicologia , Empatia
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