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1.
Childs Nerv Syst ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39207528

RESUMO

Spina bifida is a congenital neural tube closure defect, with myelomeningocele being the most clinically significant open neural tube defect occurring in one in 1000 births worldwide as reported by Phillips LA et al. (Curr Probl Pediatr Adolesc Health Care 47(7):173-177, 2017) and Zerah M and Kulkarni AV (Handb Clin Neurol 112:975-991, 2013). With advances in fetal surgery, this condition can be corrected in utero. Despite such precision surgery, many complications may still arise, with consequent spinal cord tethering being a major one. When the roots of the spinal cord adhere to the spinal canal instead of floating freely within the dural sleeve within the canal, it is termed as "tethering" as discussed by Martínez-Lage JF et al. (Neurocirugia (Astur) 18(4):312-319, 2007). Tethering has a variety of complications, which are best avoided by analyzing the outcomes of the different dural substitutes and improving surgical techniques. This literature review evaluates the use of different dural substitutes in fetal and postnatal surgery, with their effects on spinal cord tethering. Finding a significant difference in spinal cord adherence outcomes between these two groups can help one introspect on the impact of ideal surgical techniques to be implemented, thus reducing subsequent tethering and other future surgical interventions.

2.
Neurosurg Rev ; 47(1): 343, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39031287

RESUMO

To discern the efficacy of simultaneous versus delayed VPS surgery in managing hydrocephalus linked with MMC repair: The debate over the concurrent or deferred placement of ventriculoperitoneal shunts (VPS) during myelomeningocele (MMC) repair in hydrocephalic neonates necessitates a nuanced evaluation of associated risks and benefits. While VPS placement can mitigate cerebrospinal fluid (CSF) leaks and minimize wound dehiscence post-MMC repair, it concurrently introduces potential hazards such as infections and shunt-related malfunctions. This prospective cohort study focused on144 newborns with spinal myelomeningocele and hydrocephalus. Divided into two groups based on the timing of dysraphism repair and VPS placement, 101 children underwent concurrent procedures, while 43 received deferred VPS insertion post-MMC closure. Female patients constituted 60% of the cohort, with lumbar lesions being predominant. The median age for MMC closure was three days. Analysis revealed that the deferred insertion group exhibited higher rates of shunt malfunctions, CSF leaks, and wound dehiscence compared to the concurrent insertion group. Although indications hinted at a potential increase in shunt infections in the immediate insertion group, statistical significance was lacking. The study established a statistically significant association between the timing of shunt insertion during MMC repair and specific outcomes, such as CSF leaks and wound dehiscence. The findings suggest that concurrent shunt insertion during MMC repair may reduce the incidence of these complications compared to deferred insertion. However, no substantial differences emerged in terms of shunt infection and malfunction, emphasizing the persistent challenges associated with these major complications.


Assuntos
Hidrocefalia , Meningomielocele , Complicações Pós-Operatórias , Derivação Ventriculoperitoneal , Humanos , Meningomielocele/cirurgia , Meningomielocele/complicações , Hidrocefalia/cirurgia , Feminino , Derivação Ventriculoperitoneal/efeitos adversos , Recém-Nascido , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Resultado do Tratamento , Vazamento de Líquido Cefalorraquidiano , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/efeitos adversos , Lactente
3.
Sensors (Basel) ; 24(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38793979

RESUMO

The electrical protection of power networks with fault contribution from inverter-based power sources imposes new application challenges that have to be dealt with by protection engineers. This paper describes the development of a study case model of an HVDC-MMC link for testing the protection behaviour of connected converter transformers. The paper summarises the implementation and validation of the converter control as well as enhancements to provide Fault Ride-Through capability and fast fault current injection as required by the German Technical Connection Rules for HVDC. The grid code standard requires positive- and negative-sequence reactive current injection in the case of grid faults. A Doubled Decoupled Synchronous Reference Frame Phase Locked Loop (DDSRF-PLL) for Vector Current Control (VCC) is implemented. Additionally, a Fault Detection and Fault Ride-Through Reference Generator with a Current Limitation strategy is introduced. Though these techniques are well described in the literature, the DDSRF is improved for current control stability. The relationship between the parameters of the PLL and the control, as well as the behaviour of the protection system, are demonstrated. Grid faults with large voltage dips pose a significant challenge to the stability of the control system. Nevertheless, it is shown that with the developed model, it is possible to make general statements about the protection behaviour in an inverter-based environment.

4.
World J Microbiol Biotechnol ; 40(7): 225, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822208

RESUMO

Ganoderma lucidum is known for its bioactive compounds, such as polysaccharides and triterpenoids, which are crucial in food and medicine. However, liquid fermentation encounters challenges in terms of strain differentiation and stability. In this research, we employed atmospheric room temperature plasma mutation and a microbial microdroplet culture system to identify strains with enhanced biomass and triterpenoid production. The three mutant strains, YB05, YB09, and YB18, exhibited accelerated growth rates and antagonized the initial strain G0023 more effectively than the controls. Notably, YB18 displayed the fastest growth, with a 17.25% increase in colony radius. Shake flask cultivation demonstrated that, compared with the initial strain, YB05 and YB18 had 26.33% and 17.85% greater biomass, respectively. Moreover, the triterpenoid production of YB05 and YB18 surpassed that of the control by 32.10% and 15.72%, respectively, as confirmed by colorimetric detection. Importantly, these mutant strains remained stable for five generations. This study revealed a comprehensive screening system utilizing atmospheric pressure, room temperature plasma mutation technology and microbial droplet cultivation. This innovative approach offers a promising pathway for obtaining advantageous Ganoderma strains for liquid fermentation. The methodology of atmospheric room temperature plasma mutation and microbial microdroplet culture systems is detailed for better comprehension.


Assuntos
Fermentação , Mutação , Reishi , Triterpenos , Reishi/crescimento & desenvolvimento , Reishi/metabolismo , Reishi/genética , Triterpenos/metabolismo , Biomassa , Temperatura , Gases em Plasma/farmacologia
5.
Medicina (Kaunas) ; 60(3)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38541192

RESUMO

Introduction: Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older generations of these compounds, new formulations appeared on the drug market. One of them is metaphedrone (3-methylmethcathinone, 3-MMC), a structural isomer of 4-methylmethcathinone and a psychostimulant drug. Metaphedrone became popular in a large number of countries in a short period of time. The aim: The collection, analysis, and review of relevant research on the subject of metaphedrone in order to present information about the pharmacological, clinical, and toxicological profile of this compound. An assessment of the significance and role of metaphedrone in consumption patterns of novel psychoactive substances among recreational drug users. Methodology: By using search engines like Google Scholar and PubMed, the relevant literature on metaphedrone was looked for and analyzed. The search was not limited to a specific period of time. All information regarding the compound of interest was analyzed and presented. Key results and discussion: All novel psychoactive substances are abused due to their pronounced stimulatory, hallucinogenic, dissociative, and euphoric and/or relaxing characteristics. Users of 3-methylmethcathinone usually opt for this substance for recreational purposes and/or sexual stimulation. Metaphedrone has the potential to cause a psychological dependence to the users. It was determined in relevant studies that most users are from 17 to 50 years of age. Older users usually administer metaphedrone intravenously, while younger ones usually choose snorting and oral ingestion of the drug. In Serbia, metaphedrone is a legally controlled substance. The pharmacodynamic properties make metaphedrone similar to classical recreational drugs. The method of administration, mainly repeated administration in a single session, could be explained using the pharmacokinetic profile of the drug. The most reported symptoms of intoxication were those of a sympathomimetic nature, such as tachycardia, chest pain, hypertension, diaphoresis, and agitation. Most intoxications and fatal outcomes occurred to users who combined several psychoactive substances. The correlation between measured blood concentrations of the drug and outcomes of intoxication was not found. The mechanisms of metaphedrone's toxicity are not fully understood. Conclusions: There is an increasing trend of abuse of metaphedrone among recreational drugs users. Future studies should focus on pharmacological and toxicological effects of metaphedrone on animals and humans.


Assuntos
Hipertensão , Drogas Ilícitas , Metanfetamina/análogos & derivados , Humanos , Animais , Drogas Ilícitas/toxicidade , Sérvia
6.
Int Ophthalmol ; 44(1): 224, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744721

RESUMO

BACKGROUND: The pigtail was used to create an opening at the lower punctal site in grade 0 stenosis with insertion of self-retaining tube and Mitomycin C (MMC). METHODS: The patients with acquired lower punctal stenosis (grade 0) were divided randomly into equal groups, Group A: were treated with pigtail and MMC 0.02% and Group B: were treated with pigtail alone. The pigtail was inserted through the upper punctum until its tip reached the occluded punctum, this site was incised with a scalpel (No. 11). A self-retaining bicanalicular tube was then placed. RESULTS: Results of 36 eyes from 26 patients were included. No differences were observed between both groups regarding epiphora score, FDD test and punctal size preoperatively. The postoperative epiphora score, there were significant differences at 1 month (P = 0.035), 3 months (P = 0.005), and 6 months after removal (P < 0.001). The FDD test, there were significant differences at 6 months (P = 0.045), 1 month (P = 0.021), 3 months (P = 0.012), and 6 months post tube removal (P = 0.005). The punctal size, both groups differed at 1 month (P = 0.045), 3 months (P = 0.03), and 6 months post tube removal (P = 0.005). Only one case (5.5%) at each group showed extrusion of the tube. CONCLUSION: The pigtail probe, bicanalicular stent and MMC can be an effective method in treatment of severe punctal stenosis.


Assuntos
Intubação , Obstrução dos Ductos Lacrimais , Mitomicina , Humanos , Mitomicina/administração & dosagem , Masculino , Feminino , Obstrução dos Ductos Lacrimais/terapia , Obstrução dos Ductos Lacrimais/diagnóstico , Pessoa de Meia-Idade , Intubação/métodos , Intubação/instrumentação , Idoso , Resultado do Tratamento , Dacriocistorinostomia/métodos , Aparelho Lacrimal/cirurgia , Adulto , Seguimentos , Stents , Estudos Prospectivos , Alquilantes/administração & dosagem
7.
Development ; 147(23)2020 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-33158925

RESUMO

In higher plants, the female germline is formed from the megaspore mother cell (MMC), a single cell in the premeiotic ovule. Previously, it was reported that mutants in the RNA-dependent DNA methylation (RdDM) pathway might be involved in restricting the female germline to a single nucellus cell. We show that the DRM methyltransferase double mutant drm1drm2 also presents ectopic enlarged cells, consistent with supernumerary MMC-like cells. In wild-type ovules, MMC differentiation requires SPOROCYTELESS/NOZZLE (SPL/NZZ), as demonstrated by the spl/nzz mutant failing to develop an MMC. We address the poorly understood upstream regulation of SPL/NZZ in ovules, showing that the RdDM pathway is important to restrict SPL/NZZ expression. In ago9, rdr6 and drm1drm2 mutants, SPL/NZZ is expressed ectopically, suggesting that the multiple MMC-like cells observed might be attributable to the ectopic expression of SPL/NZZ. We show that the ovule identity gene, SEEDSTICK, directly regulates AGO9 and RDR6 expression in the ovule and therefore indirectly regulates SPL/NZZ expression. A model is presented describing the network required to restrict SPL/NZZ expression to specify a single MMC.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Metilação de DNA/genética , Proteínas de Domínio MADS/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas Argonautas/genética , Regulação da Expressão Gênica de Plantas/genética , Células Germinativas/crescimento & desenvolvimento , Células Germinativas/metabolismo , Metiltransferases/genética , Mutação/genética , Óvulo Vegetal/genética , Desenvolvimento Vegetal/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , RNA/genética , RNA Polimerase Dependente de RNA/genética , Células-Tronco/citologia
8.
BMC Musculoskelet Disord ; 24(1): 545, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400860

RESUMO

BACKGROUND: Individuals with myelomeningocele (MMC) exhibit neurological deficits below the lesion level involving both motor and sensory functions. Ambulation and functional outcomes in patients offered orthotic management since childhood were investigated. METHODS: Physical function, physical activity, pain, and health status were assessed in a descriptive study. RESULTS: Of 59 adults with MMC, aged 18-33 years, 12 were in the community ambulation (Ca), 19 in the household ambulation (Ha), six in the non-functional (N-f), and 22 in the non-ambulation (N-a) groups. Orthoses were used by 78% (n = 46), i.e., by 10/12 in the Ca, 17/19 in the Ha, 6/6 in the N-f, and 13/22 in the N-a groups. In the ten-metre walking test, the non-orthosis group (NO) walked faster than those wearing ankle-foot orthoses (AFOs) or free-articulated knee-ankle-foot orthoses (KAFO-Fs), the Ca group faster than the Ha and N-f groups, and the Ha group faster than the N-f group. In the six-minute walking test, the Ca group walked farther than the Ha group. In the five times sit-to-stand test, the AFO and KAFO-F groups required longer than the NO group, and the KAFO-F group longer than the foot orthosis (FO) group. Lower extremity function with orthoses was higher in the FO than the AFO and KAFO-F groups, higher in the KAFO-F than the AFO group, and higher in the AFO group than in those using trunk-hip-knee-ankle-foot orthoses. Functional independence increased with ambulatory function. Time spent in physical recreation was higher in the Ha than the Ca and N-a groups. There were no differences between the ambulation groups in rated pain or reported health status. CONCLUSION: The physical function results in persons with MMC improve our understanding of this population's heterogeneity and shed light on the importance of individualized orthotic management. The similarities between the various ambulatory levels in physical activity, pain, and health status may mirror opportunities to achieve equal results regardless of disability level. A clinical implication of the study is that orthotic management is likely to be beneficial for the patient with MMC of which the majority used their orthoses for most time of the day.


Assuntos
Órtoses do Pé , Meningomielocele , Humanos , Adulto , Criança , Meningomielocele/complicações , Meningomielocele/terapia , Caminhada , Aparelhos Ortopédicos , Dor , Nível de Saúde , Marcha
9.
Sensors (Basel) ; 24(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38203001

RESUMO

The recent oscillation events in offshore wind farms (OWFs) connected via a modular multilevel-converter-based HVDC (MMC-HVDC) system are developing towards a wider frequency band, which causes complex a small-signal interaction phenomenon and difficulties in the stability analysis and control. In this paper, the wideband dynamic interaction mechanism is investigated based on the impedance analysis method and an improved control strategy using an optimization algorithm is proposed to improve the small-signal stability and reduce the oscillation risks. First, the detailed impedance models of the grid-connected system are established considering the distribution characteristics of the submarine cable, control delay and frequency coupling effect. Then, combined with the active damping control method, the wideband resonance mechanism is analyzed, and the stability constraints of controller parameters are obtained using the impedance stability criterion. Finally, an improved multi-objective slime mold algorithm (MOSMA)-based coordinated optimization control strategy is proposed to enhance the adaptability of the controller parameters and the wideband damping ability of a grid-connected system, which can improve the wideband stability of the system. The simulation and experimental results verify the proposed control strategy.

10.
Int J Mol Sci ; 24(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37373041

RESUMO

Mast cells (MCs) are involved in several immune-related responses, including those in bacterial infections, autoimmune diseases, inflammatory bowel diseases, and cancer, among others. MCs identify microorganisms by pattern recognition receptors (PRRs), activating a secretory response. Interleukin (IL)-10 has been described as an important modulator of MC responses; however, its role in PRR-mediated activation of MC is not fully understood. We analyzed the activation of TLR2, TLR4, TLR7 and Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in mucosal-like MCs (MLMCs) and peritoneum-derived cultured MCs (PCMCs) from IL-10-/- and wild-type (WT) mice. IL-10-/- mice showed a reduced expression of TLR4 and NOD2 at week 6 and TLR7 at week 20 in MLMC. In MLMC and PCMC, TLR2 activation induced a reduced secretion of IL-6 and TNFα in IL-10-/- MCs. TLR4- and TLR7-mediated secretion of IL-6 and TNFα was not detected in PCMCs. Finally, no cytokine release was induced by NOD2 ligand, and responses to TLR2 and TLR4 were lower in MCs at 20 weeks. These findings indicate that PRR activation in MCs depends on the phenotype, ligand, age, and IL-10.


Assuntos
Interleucina-10 , Interleucina-6 , Animais , Camundongos , Citocinas/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Ligantes , Mastócitos/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Receptores de Reconhecimento de Padrão/genética , Receptores de Reconhecimento de Padrão/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 7 Toll-Like/metabolismo
11.
Int J Mol Sci ; 24(12)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37373293

RESUMO

The melanocortin receptors are involved in numerous physiological pathways, including appetite, skin and hair pigmentation, and steroidogenesis. In particular, the melanocortin-3 receptor (MC3R) is involved in fat storage, food intake, and energy homeostasis. Small-molecule ligands developed for the MC3R may serve as therapeutic lead compounds for treating disease states of energy disequilibrium. Herein, three previously reported pyrrolidine bis-cyclic guanidine compounds with five sites for molecular diversity (R1-R5) were subjected to parallel structure-activity relationship studies to identify the common pharmacophore of this scaffold series required for full agonism at the MC3R. The R2, R3, and R5 positions were required for full MC3R efficacy, while truncation of either the R1 or R4 positions in all three compounds resulted in full MC3R agonists. Two additional fragments, featuring molecular weights below 300 Da, were also identified that possessed full agonist efficacy and micromolar potencies at the mMC5R. These SAR experiments may be useful in generating new small-molecule ligands and chemical probes for the melanocortin receptors to help elucidate their roles in vivo and as therapeutic lead compounds.


Assuntos
Farmacóforo , Receptor Tipo 3 de Melanocortina , Receptor Tipo 3 de Melanocortina/agonistas , Receptor Tipo 3 de Melanocortina/metabolismo , Guanidina/farmacologia , Ligantes , Receptores de Melanocortina/metabolismo , Guanidinas , Relação Estrutura-Atividade
12.
Int J Mol Sci ; 24(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37446306

RESUMO

Fanconi anemia (FA) develops due to a mutation in one of the FANC genes that are involved in the repair of interstrand crosslinks (ICLs). FANCG, a member of the FA core complex, is essential for ICL repair. Previous FANCG-deficient mouse models were generated with drug-based selection cassettes in mixed mice backgrounds, leading to a disparity in the interpretation of genotype-related phenotype. We created a Fancg-KO (KO) mouse model using CRISPR/Cas9 to exclude these confounders. The entire Fancg locus was targeted and maintained on the immunological well-characterized C57BL/6J background. The intercrossing of heterozygous mice resulted in sub-Mendelian numbers of homozygous mice, suggesting the loss of FANCG can be embryonically lethal. KO mice displayed infertility and hypogonadism, but no other developmental problems. Bone marrow analysis revealed a defect in various hematopoietic stem and progenitor subsets with a bias towards myelopoiesis. Cell lines derived from Fancg-KO mice were hypersensitive to the crosslinking agents cisplatin and Mitomycin C, and Fancg-KO mouse embryonic fibroblasts (MEFs) displayed increased γ-H2AX upon cisplatin treatment. The reconstitution of these MEFs with Fancg cDNA corrected for the ICL hypersensitivity. This project provides a new, genetically, and immunologically well-defined Fancg-KO mouse model for further in vivo and in vitro studies on FANCG and ICL repair.


Assuntos
Cisplatino , Anemia de Fanconi , Humanos , Animais , Camundongos , Cisplatino/metabolismo , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Camundongos Endogâmicos C57BL , Sistemas CRISPR-Cas , Proteínas de Ligação a DNA/metabolismo , Fibroblastos/metabolismo , Mitomicina , Fenótipo , Proteína do Grupo de Complementação G da Anemia de Fanconi/genética
13.
Afr J AIDS Res ; 22(4): 327-333, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38117746

RESUMO

South Africa's 2016 medical male circumcision (MMC) guidelines ("the guidelines") provide direction for the MMC programme's implementation in South Africa. The aim of our document analysis was to assess the guidelines, particularly in lieu of changing guidance from WHO and PEPFAR. We then assessed how the guidelines might be applied to infant and child male circumcision (ICMC). The analysis was performed by reviewing South Africa's guidelines, along with international documents used in developing those guidelines, to identify the historical development of the guidelines, as well as the implications for MMC and ICMC decision-making within the South African context. The following principles were analysed within the context of South Africa's guidelines: (1) quality and safety; (2) informed consent; (3) confidentiality; (4) human rights; and (5) accessibility of services. Tthe document analysis also identified ambiguities that exist in the guidelines, particularly regarding consent, recognising religious or cultural exemptions, and guaranteeing the best interests of the child. South Africa's MMC guidelines could benefit from incorporating common definitions to assist with interpretation and understanding, thus preventing confusion and controversy among programme planners, parents and boys. The guidelines were made available in 2016 and recommendations for circumcision have evolved as new research and information has become available. South Africa's National Department of Health should review and update these guidelines, with a focus on both MMC and ICMC issues, so that they reflect the most up-to-date, accurate information available, to avoid inconsistent practices, risks, and litigation in the management of the programme. This study was situated within a qualitative paradigm and applied a social choice theory perspective to make sense of the MMC guidelines. The study concludes that future policy revisions should develop a broader understanding of the complex medical male circumcision decision-making process, particularly faced by parents.


Assuntos
Circuncisão Masculina , Infecções por HIV , Lactente , Criança , Humanos , Masculino , África do Sul , Infecções por HIV/prevenção & controle , Análise Documental , Direitos Humanos
14.
Int Ophthalmol ; 43(11): 4225-4233, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37561247

RESUMO

PURPOSE: To investigate the long-term efficacy and safety of the novel method sutureless trabeculectomy with topical administration of bevacizumab. MATERIALS/METHODS: Primary open-angle glaucoma patients with intraocular pressure (IOP) > 21 mmHg despite maximum tolerated medication were included in a single-blind prospective interventional clinical trial. Group 1 underwent sutureless scleral tunnel trabeculectomy with intraoperative topical administration of bevacizumab (1.25 mg) applied on the scleral incision for 1 min. Group 2 underwent sutureless trabeculectomy alone and group 3 (control group) underwent conventional trabeculectomy with mitomycin C (MMC). Outcome measures were surgical success, IOP, number of needed anti-glaucoma medications, and complications. Patients were followed for two years. RESULTS: Finally, 50 eyes from group 1, 46 from group 2, and 47 from group 3 were analyzed. At the end of 24 months, 52% (n = 26) of group 1, 34.8% (n = 16) of group 2, and 57.4% (n = 27) of group 3 had complete success (IOP < 18 mmHg without medication). The difference was only significant between groups 2 and 3 (p = 0.003). 94% (n = 47) of group 1, 89.1% (n = 41) of group 2, and 91.5% (n = 43) of group 3 had qualified success (IOP < 18 mmHg with ≤ 2 anti-glaucoma medications) (p = 0.69). There was a significant difference in the overall IOP mean between the three groups (p < 0.0001). There was no significant difference between the three groups in complication rates and the number of needed anti-glaucoma medications for IOP control. CONCLUSION: Sutureless trabeculectomy with topical application of bevacizumab showed comparable surgical success rates with conventional trabeculectomy and MMC in long-term follow-up. Additionally, adjuvant use of topical bevacizumab had a significant positive impact on long-term IOP control.


Assuntos
Glaucoma de Ângulo Aberto , Trabeculectomia , Humanos , Agentes Antiglaucoma , Bevacizumab/uso terapêutico , Seguimentos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular , Mitomicina , Estudos Prospectivos , Método Simples-Cego , Trabeculectomia/métodos , Resultado do Tratamento
15.
Protein Expr Purif ; 192: 106030, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34920133

RESUMO

Nanobodies (Nbs) are single-domain antibodies, which have potential application value in tumor-targeted therapy, immunotherapy, diagnostic probe, and molecular imaging. Typically, Nbs are captured by affinity chromatography via the addition of specific fusion tags at their N or C terminus. Nerve growth factor (NGF), which regulates the growth and development of peripheral and central neurons, maintains neuronal survival and plays a key role in both arthritis and acute and chronic pain. In this study, a method for capture and purification of an untagged Nb (anti-NGF Nb) by mixed weak cation chromatography and cation exchange chromatography was established. First, pH 4.0-5.0 was demonstrated to be the optimal loading condition for Capto MMC to capture anti-NGF by the design of experiments (DOE). Furthermore, high purity and yield products can be obtained at laboratory scale and commercial production scale by adjusting the protein pH. Additionally, direct capture of anti-NGF Nb using Capto MMC without adjusting anti-NGF Nb harvest pH was investigated. The anti-NGF Nb captured by Capto MMC was 67.2% yield, 94.5% monomer purity, and host cell protein (HCP) was reduced from 74,931 ppm to 484 ppm. The anti-NGF Nb that were further purified using Capto S ImpAct achieved 84.5% yield and 99.2% purity and 77 ppm of HCP. The scaling-up process was consistent with the results of the optimized process, further demonstrating the feasibility of this method. This outcome provides a highly promising and competitive alternative to affinity chromatography-based processing strategies for Nbs.


Assuntos
Cromatografia por Troca Iônica/métodos , Anticorpos de Cadeia Única/isolamento & purificação , Adsorção , Resinas de Troca de Cátion/química , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/metabolismo
16.
Drug Chem Toxicol ; : 1-10, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36476306

RESUMO

This study aimed to evaluate the effect of aqueous and acetone extracts from Artemisia vulgaris L. (AV) and Artemisia alba Turra (AA), and two major polyphenols compounds (3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside) presented in both extracts of the plants against mitomycin C (MMC)-induced genomic instability. Genomic instability was measured using cytokinesis block micronucleus (MN) assay in human peripheral blood lymphocytes (PBLs) in vitro by analyzing two biomarkers - MN and nuclear division index (NDI). Extracts were tested in a concentration-dependent manner (10-250 µg/mL), while 3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside were tested in three different concentrations, in combination with 0.5 µg/mL of MMC. Aqueous and acetone extracts obtained from both plants significantly reduced MMC-induced MN frequency in PBLs, compared to positive control cells (p < 0.05). Extracts from AV did not affect NDI, whereas the concentrations of 10-100 µg/mL of aqueous and acetone AA extracts significantly elevated MMC-decreased NDI values in comparison to positive control cells (p < 0.05). Combined treatment of 3,5-dihydroxybenzoic acid and MMC showed a significant reduction of MMC-induced MN frequency, while quercetin-3-O-glucopyranoside increased MN frequency compared to positive control cells (p < 0.05). Both compounds decreased NDI values but only at the highest tested concentration of quercetin-3-O-glucopyranoside it was of greater significance. In conclusion, all extracts from AV and AA and 3,5-dihydroxybenzoic acid showed protective effect, whereby aqueous AA demonstrated the highest protective effect on MMC- induced genomic instability, while quercetin-3-O-glucopyranoside showed co-mutagen effect.

17.
Sensors (Basel) ; 23(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36616744

RESUMO

In order to make the grid-connected composite device (GCCD) controller meet the requirements of different operating modes and complex working conditions of power grid, this paper proposes to introduce sliding mode control (SMC) into GCCD controller. Firstly, the mathematical model of MMC converter is established, and the sliding mode controller is designed based on the SMC principle. Then, aiming at the problems of complex controller structure and difficult parameter tuning in multiple modes of the GCCD, this paper proposes a controller parameter optimization method based on improved Month Flame optimization (IMFO) algorithm. This method improves the MFO algorithm by introducing good point set (GPS) initialization and Levy flight strategy, which accelerates the convergence speed of the algorithm while avoiding falling into local optimization, and realizes the optimization of converter controller parameters. Under a variety of standard test functions, the advantages of the proposed IMFO algorithm are verified by comparing it with the traditional algorithm. Finally, in order to realize the automatic tuning of control parameters, the Python-PSCAD joint simulation method is studied and implemented. Taking the comprehensive integral of time and absolute error (CITAE) index as the objective function, the parameters of the sliding mode controller are optimized. The simulation results show that the controller parameters optimized by the IMFO algorithm can make the GCCD have better dynamic performance.

18.
Sensors (Basel) ; 22(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35009901

RESUMO

Open circuit failure mode in insulated-gate bipolar transistors (IGBT) is one of the most common faults in modular multilevel converters (MMCs). Several techniques for MMC fault diagnosis based on threshold parameters have been proposed, but very few studies have considered artificial intelligence (AI) techniques. Using thresholds has the difficulty of selecting suitable threshold values for different operating conditions. In addition, very little attention has been paid to the importance of developing fast and accurate techniques for the real-life application of open-circuit failures of IGBT fault diagnosis. To achieve high classification accuracy and reduced computation time, a fault diagnosis framework with a combination of the AC-side three-phase current, and the upper and lower bridges' currents of the MMCs to automatically classify health conditions of MMCs is proposed. In this framework, the principal component analysis (PCA) is used for feature extraction. Then, two classification algorithms-multiclass support vector machine (SVM) based on error-correcting output codes (ECOC) and multinomial logistic regression (MLR)-are used for classification. The effectiveness of the proposed framework is validated by a two-terminal simulation model of the MMC-high-voltage direct current (HVDC) transmission power system using PSCAD/EMTDC software. The simulation results demonstrate that the proposed framework is highly effective in diagnosing the health conditions of MMCs compared to recently published results.


Assuntos
Inteligência Artificial , Máquina de Vetores de Suporte , Algoritmos , Simulação por Computador , Análise de Componente Principal
19.
Int J Mol Sci ; 24(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36614155

RESUMO

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN.


Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Humanos , Antineoplásicos/uso terapêutico , Interferon alfa-2 , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Inquéritos e Questionários , Carcinoma de Células Escamosas/tratamento farmacológico
20.
J Therm Spray Technol ; 31(1-2): 102-118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38624954

RESUMO

This study developed microstructure-based finite element (FE) models to investigate the behavior of cold-sprayed aluminum-alumina (Al-Al2O3) metal matrix composite (MMC) coatings subject to indentation and quasi-static compression loading. Based on microstructural features (i.e., particle weight fraction, particle size, and porosity) of the MMC coatings, 3D representative volume elements (RVEs) were generated by using Digimat software and then imported into ABAQUS/Explicit. State-of-the-art physics-based modeling approaches were incorporated into the model to account for particle cracking, interface debonding, and ductile failure of the matrix. This allowed for analysis and informing on the deformation and failure responses. The model was validated with experimental results for cold-sprayed Al-34 wt.% Al2O3 and Al-46 wt.% Al2O3 metal matrix composite coatings under quasi-static compression by comparing the stress versus strain histories and observed failure mechanisms (e.g., matrix ductile failure). The results showed that the computational framework is able to capture the response of this cold-sprayed material system under compression and indentation, both qualitatively and quantitatively. The outcomes of this work have implications for extending the model to materials design and for applications involving different types of loading in real-world application (e.g., erosion and fatigue).

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